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Higher omega-6:omega-3 ratios may be associated with progressive increases in TNF-α and interleukin-6 levels as depressive symptoms increase. (2007) www.sciencedaily.com
From the article:
The study, conducted in OSU’s Institute for Behavioral Medicine Research, focused on a group of 43 middle-aged to elderly men and women, nearly half of which were the caregiver spouses of people with Alzheimer’s or other dementias. By including caregivers who typically report greater stress and more depression than similar ad ults who are not caregiving, the researchers could look at how depression and diet might interact to affect inflammation.
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The analysis showed that participants who had much more omega-6 – compared to omega-3 – fatty acids, and who also were reporting more symptoms of depression, had much higher levels of IL-6 and TNF-alpha, two cytokines which enhance inflammation.
“The data suggest that higher depression and a poorer diet in terms of omega-3 can work together to promote inflammation. Other researchers have shown that clinically depressed people – those with more severe depression – often have lower omega-3 levels in their blood, and several studies have shown that supplementing diets with omega-3 improves depression,” Kiecolt-Glaser said, although the reason isn’t clear.
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“This study has shown that even in people who did not take supplements, maybe just a little bit more omega-3, could help reduce their markers for both stress and depression,” Belury said.
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Omega-3 supplementation altered interleukin-6 levels by -12% (vs +36% in placebo group) and TNF-α by -2.3% (vs +12% in placebo group). (2012) www.sciencedaily.com
From the article:
The scientists recruited 138 adults – 45 men and 93 women – who were in good health, but who were either overweight or obese and lived sedentary lives. Their average age was 51 years. Based on body mass index, a measure of weight relative to height, 91 percent of the participants were overweight and 47 percent were obese.
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Participants received either a placebo or one of two different doses of omega-3 fatty acids – either 2.5 grams or 1.25 grams per day. The supplements were calibrated to contain a ratio of the two fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than does DHA.
After four months, participants who had taken the omega-3 supplements had significantly lower levels in their blood of two proteins that are markers of inflammation, also called pro-inflammatory cytokines. The low-dose group showed an average 10 percent decrease in the cytokine interleukin-6 (IL-6), and the high-dose group’s overall IL-6 dropped by 12 percent. In comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.
Levels of the cytokine tumor necrosis factor-alpha (TNF-a) also dropped, but in a more modest way, by 0.2 percent and 2.3 percent in the low- and high-dose groups, respectively. The placebo group’s TNF-a increased by an average of 12 percent.
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Interleukin-6 (IL-6) acutely and directly induces hyperexcitability associated with epilepsy and autism in rat brain. (2012) www.sciencedaily.com
From the article:
Garcia and Atzori hypothesized that the protein IL-6 acutely and directly induces hyper-excitability by altering the balance between excitation and inhibition within synaptic communication. In other words, IL-6 is not just present when hyper-excitability occurs in the nervous system. It may actually cause it in some circumstances, Garcia said.
The UT Dallas research team administered IL-6 to rat brain tissue and monitored its synaptic excitability. The brain tissue exhibited higher than normal excitability in their synapses, a symptom that may lead to misfiring of signals in epilepsy and other conditions.
The researchers then injected sgp130 -a novel drug that acts as an IL-6 blocker- into the laboratory animals' brains. The substance limited excitability and appeared to prevent the conditions that lead to related neurological and psychiatric disorders, Garcia said.
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Infection-induced interleukin-6 secretion in mice increases the risk for schizophrenia- and autism-like behaviors in offspring. (2007) www.sciencedaily.com
From the article:
It has been known for some time that schizophrenia is more common among people born in the winter and spring months, as well as in people born following influenza epidemics. Recent studies suggest that if a woman suffers even one respiratory infection during her second trimester, her offspring’s risk of schizophrenia rises by three to seven times.
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To prove this, they triggered an artificial immune response in pregnant mice–giving them a faux case of the flu. The trigger they used was a snippet of double-stranded RNA called poly(I:C), which fools the immune system into thinking there has been an infection by an RNA virus.
A single, mid-gestation injection of poly(I:C) creates a strong immune response in a pregnant mouse. When her offspring reach adulthood, they display behavioral and tissue abnormalities similar to those seen in schizophrenia in humans.
Though there might be some disagreement over what it means for a mouse to be schizophrenic, these abnormalities are generally marked by inappropriateness of response and difficulty in coping.
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The team tried injecting the pregnant mice with individual cytokines, rather than with poly(I:C). It turned out that after a single dose of a specific cytokine known as interleukin-6 (or IL-6), a mouse would give birth to offspring who, at maturity, exhibited the familiar schizophrenia- and autism-like behaviors.
To confirm the role of IL-6, Steve Smith, the lead researcher, gave fake colds (poly(I:C)) to two groups of pregnant, IL-6-free mice. One group had received anti-IL-6 antibodies which blocked IL-6; the other consisted of so-called IL-6 knockout mice (mice whose genetic makeup prevents them from synthesizing IL-6). In both groups, offspring grew up normal, showing that IL-6 is necessary for the maternal poly(I:C) treatment to alter fetal brain development and subsequent behavior in the offspring.
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Interleukin-6, CRP and triglycerides are likely shared causal risk factors for depression and coronary heart disease. (2019) www.sciencedaily.com
From the article:
Together, these results suggest that the link between heart disease and depression cannot be explained by a common genetic predisposition to the two diseases. Instead, it implies that something about an individual’s environment – such as the risk factors they are exposed to – not only increases their risk of heart disease, but at the same time increases their risk of depression.
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Of these common biomarkers, they found that triglycerides (a type of fat found in the blood) and the inflammation-related proteins IL-6 and CRP were also risk factors for depression.
Both IL-6 and CRP are inflammatory markers that are produced in response to damaging stimuli, such as infection, stress or smoking. Studies by Dr Khandaker and others have previously shown that people with elevated levels of IL-6 and CRP in the blood are more prone to develop depression, and that levels of these biomarkers are high in some patients during acute depressive episode. Elevated markers of inflammation are also seen in people with treatment resistant depression. This has raised the prospect that anti-inflammatory drugs might be used to treat some patients with depression. Dr Khandaker is currently involved in a clinical trial to test tocilizumab, an anti-inflammatory drug used for the treatment of rheumatoid arthritis that inhibits IL-6, to see if reducing inflammation leads to improvement in mood and cognitive function in patients with depression.
While the link between triglycerides and coronary heart disease is well documented, it is not clear why they, too, should contribute to depression. The link is unlikely to be related by obesity, for example, as this study has found no evidence for a causal link between body mass index (BMI) and depression.
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Maternal immune activation during pregnancy is associated with changes in the newborns' stimulus processing and long-term development. (2018) www.sciencedaily.com
From the article:
Blood drawn from mothers during their third trimester was tested for levels of IL-6 and CRP – two proteins that are found at higher levels when the immune system is activated. Peterson’s team also monitored fetal heart rate as an indicator for nervous system development. The team found that CRP did correlate with variability of the fetal heart rate, which is influenced heavily by the nervous system, indicating that maternal inflammation was already beginning to shape brain development.
When the babies were born, they were given MRI scans in their first few weeks of life, providing researchers a unique view of early neural development and the influence of prenatal factors. Brain imaging revealed a striking finding – significant changes in the communication between specific brain regions correlated with elevated maternal IL-6 and CRP levels. These brain regions are known collectively as the salience network, whose job is to filter stimuli coming into the brain and determine which deserve attention.
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“The salience network sifts through that information and decides what is important and warrants action.” Disturbances in the functioning of this network, as well as various kind of infection and other triggers of a pregnant woman’s immune response, have been linked to development of psychiatric illnesses, such as schizophrenia and autism spectrum disorders.
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The correlations of elevated maternal inflammatory markers were not limited to the newborn period, but continued to persist into toddlerhood. When the babies turned 14 months of age, researchers assessed them for motor skills, language development, and behavior. Following the established Bayley Scales of Infant and Toddler Development-Third Edition, Peterson found significant changes in the scores of toddlers born to mothers with elevated levels of both IL-6 and CRP.
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Higher maternal interleukin-6 (IL-6) levels are associated with changes in the newborn amygdala leading to altered impulse control. (2017) www.sciencedaily.com
From the article:
“We discovered that higher levels of interleukin-6, an inflammatory marker, were associated with changes in the neonatal amygdala in terms of its anatomy and connectivity. Furthermore, our subsequent findings showed that these changes were also associated with lower impulse control at 2 years of age,” explains Prof. Buß. “We therefore conclude that a link exists between higher levels of maternal inflammatory markers and an increased risk of psychiatric disorders that are commonly associated with impaired impulse control.” Animal models have shown that infections and inflammation in the pregnant animal lead to both changes in offspring brain development and behavior. Epidemiological studies also support the findings of this study, suggesting that maternal infections and other clinical phenotypes associated with increased interleukin-6 concentrations (such as obesity) during pregnancy increase the risk of psychiatric disorders such as schizophrenia and autism.
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Stress-induced chronic inflammation is associated with depression and other diseases. (2015) www.sciencedaily.com
From the article:
The authors found that in addition to being linked to numerous physical health issues, including cancer and diabetes, systemic inflammation is linked to mental health issues such as depression. Among patients suffering from clinical depression, concentrations of two inflammatory markers, CRP and IL-6, were elevated by up to 50 percent.
Fagundes said chronic inflammation is most common in individuals who have experienced stress in their lives, including lower socio-economic status or those who experienced abuse or neglect as children. Other contributing factors are a high-fat diet and high body mass index.
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The study also found that depression caused by chronic inflammation is resistant to traditional therapy methods, but can be treated with activities such as yoga, meditation NSAIDS and exercise.
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Interleukin-6 (IL-6) may play a causal role in the increased ischemic damage after stroke associated with social isolation in mice. (2009) www.sciencedaily.com
From the article:
Researchers at Ohio State University found that all the male mice that lived with a female partner survived seven days after a stroke, but only 40 percent of socially isolated animals lived that long.
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The amount of tissue damage in the brain was about four times larger in the mice housed alone compared to those housed with another mouse.
“The number of neurons dying is significantly decreased in the pair-housed mice,” DeVries said.
In addition, socially housed mice had significantly less edema, or excess water in the brain, when compared to the isolated animals.
“In clinical stroke, edema is a major concern because it can lead to additional neuronal damage, so it is significant that pair housing reduced edema,” Karelina said.
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In addition, findings revealed that mice that lived with others had significantly higher levels of a cytokine in their brain called interleukin-6 (IL-6) that has an anti-inflammatory response in the brain, helping to limit damage caused by the stroke.
The finding about IL-6 is especially interesting, Karelina said, because IL-6 appears to have opposite effects in the brain than it does in the rest of the body.
“IL-6 reduces inflammation in the brain, so it is protective in a stroke, but it is a pro-inflammatory in the periphery of the body,” Karelina said.
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Blockade of IL-6 receptor improved cognition in patients with schizophrenia. (2016) www.sciencedaily.com
From the article:
After just two intravenous doses in eight weeks of tocilizumab, an immune-suppressing drug regularly prescribed for rheumatoid and juvenile arthritis, study participants had significantly improved cognitive ability, said Dr. Brian J. Miller, a psychiatrist at the Medical College of Georgia at Augusta University.
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Anywhere from 25 to 50 percent of patients may have inflammation in the brain contributing to that dysfunction. Problems range from having trouble remembering important numbers to impairment of executive function that enables them to analyze, organize, and generally manage their lives.
Tocilizumab targets the receptor for IL-6, a protein which helps regulate inflammation that is often elevated in patients with schizophrenia. Higher IL-6 levels also have been correlated with a smaller hippocampus, a center for learning and memory in the brain, as well as experiencing more psychiatric symptoms.
The five study patients did not experience improvement in overall levels of psychiatric symptoms, such as hallucinations and delusions, more classic symptoms of schizophrenia, which were already well-controlled with antipsychotics, Miller said.
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Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and negatively correlates with offspring working memory. (2018) www.sciencedaily.com
From the article:
[…] collected blood samples from 84 expectant mothers at each pregnancy trimester. The samples were measured for levels of the cytokine interleukin-6, or IL-6, an inflammatory marker known to play a role in fetal brain development.
Four weeks following birth, brain connectivity patterns of the offspring were assessed using functional magnetic resonance imaging, or fMRI, scans. At age 2, the children were also tested for working memory performance, a key skill that supports academic achievement and is frequently compromised in mental health disorders.
The data from mother and child show that differences in the levels of inflammatory markers are directly associated with differences in newborn brain communication, and later to working memory scores at age 2. Higher levels of the marker during pregnancy tended to result in less working memory capacity in the child.
“Importantly, this doesn’t mean that every exposure to inflammation will result in a negative impact to the child; however, these findings provide new avenues for research, and can help health care providers think about how, and when, inflammation might impact a child’s long-term learning development and mental health,” said Alice Graham, Ph.D., postdoctoral fellow in behavioral neuroscience in the OHSU School of Medicine.
A notable aspect of the study, according to Graham, is the development of a model that can accurately estimate information about maternal inflammation during pregnancy based only on newborn brain functioning.
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Interleukin-6 (IL-6) mediates delirium-like phenotypes in a mouse model of urinary tract infection. (2021) www.sciencedaily.com
From the article:
In a Y-shaped maze with three arms to explore, uninfected mice tended to explore all three arms, while mice with UTIs [urinary tract infection] kept returning to the same one, suggesting a lapse in short-term memory, another feature of delirium.
The investigators also observed structural changes in the brains of mice with UTIs.
In a previous study led by Lahiri, published in February in the American Journal of Respiratory Cell and Molecular Biology, investigators found a connection between ventilator-induced lung injury and delirium. Lahiri and colleagues theorized that in both cases this was because of the reaction of IL-6, which helps regulate immune response, to the lung injury or the UTI.
“Occasionally, when the response of IL-6 is excessive, our research indicates that there can be brain injury,” Lahiri said. “IL-6 induces changes within the neurons that our studies connected with delirium-like behavior. This is the first time this type of structural and functional change has been demonstrated. We’ve now shown two distinct models of this connection, one non-infectious and one infectious.”
In the current study, when investigators treated some of the infected mice with antibodies that blocked the effects of IL-6, the delirium-like behavior of those animals resolved. “Treatment with anti-IL-6 antibody in the UTI group normalized all the brain changes, both structural and functional,” Lahiri said. “A wealth of studies have shown a link between IL-6 and delirium, but only this study and our previous study have shown that IL-6 may play a direct pathological role in delirium.”
If symptoms are treated early, he added, full recovery is possible, and the next step is to design clinical trials with anti-IL-6 antibodies as a treatment for patients with UTI-induced delirium.
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Intranasally administered interleukin-6 (IL-6) helps the brain retain emotional and procedural memories during REM sleep. (2009) www.sciencedaily.com
From the article:
“Here, we provide the first evidence that the immunoregulatory signal interleukin-6 plays a beneficial role in sleep-dependent formation of long-term memory in humans.”
To make this discovery, Marshall and colleagues had 17 healthy young men spend two nights in the laboratory. On each night after reading either an emotional or neutral short story, they sprayed a fluid into their nostrils which contained either interleukin-6 or a placebo fluid. The subsequent sleep and brain electric activity was monitored throughout the night. The next morning subjects wrote down as many words as they could remember from each of the two stories. Those who received the dose of IL-6 could remember more words.
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Social rank and rank uncertainty predicted levels of the pro-inflammatory proteins CRP, IL-6 and TNF-alpha in monkeys. (2016) www.sciencedaily.com
From the article
The team found that social rank and rank uncertainty predicted key risk factors for poor health, specifically pro-inflammatory proteins (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) which are risk factors for chronic diseases such as cardiovascular disease and diabetes.
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The researchers discovered that high ranking monkeys with low certainty of their social status showed higher markers of inflammation, which can be a sign of a chronic disease state such as diabetes, than those with very certain status. So high-ranking monkeys may experience some health risks, but only when their position is questionable and they are consequently at risk of losing their status.
The opposite pattern was found for low ranking monkeys – high dominance certainty was associated with higher markers of inflammation, whereas low certainty was associated with lower levels of inflammatory proteins. Monkeys that are uncertain in their low rank might have opportunities for upward mobility in the hierarchy, which may be associated with better health outcomes.
Vandeleest said the results of the study show that status uncertainty alone may be a risk factor for acute diseases. The results also indicate that uncertainty in status over longer periods in relationship to rank are related to chronic disease states as well.
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Exercise protected mice from toxin-induced hippocampal damage by stimulating the production of interleukin-6 in the brain. (2011) www.sciencedaily.com
From the article:
Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults. The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.
Pharmacological therapies to downregulate inflammation and address cognitive decline in older adults, and those with Alzheimer’s disease, have been less successful. This research helps understand how exercise could be used to affect the path of many human conditions, such as neurodevelopmental disorders and neurodegenerative diseases. In addition, as a chemical model of neuronal damage was used, it also raises the possibility that exercise could offer protection against the potentially harmful effects of environmental toxins.
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Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014) www.sciencedaily.com
From the article:
Now, researchers have carried out the first ever longitudinal study – a study that follows the same cohort of people over a long period of time – to examine the link between these markers [cytokines such as interleukin-6] in childhood and subsequent mental illness.
A team of scientists led by the University of Cambridge studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children – also known as Children of the 90s – taking blood samples at age 9 and following up at age 18 to see if they had experienced episodes of depression or psychosis. The team divided the individuals into three groups, depending on whether their everyday levels of IL-6 were low, medium or high. They found that those children in the ‘high’ group were nearly two times more likely to have experienced depression or psychosis than those in the ‘low’ group.
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The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. People with depression and schizophrenia are known to have a much higher risk of developing heart disease and diabetes, and elevated levels of IL-6 have previously been shown to increase the risk of heart disease and type 2 diabetes.
Professor Peter Jones, Head of the Department of Psychiatry and senior author of the study, says: “Inflammation may be a common mechanism that influences both our physical and mental health. It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.”
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This potential common mechanism could help explain why physical exercise and diet, classic ways of reducing risk of heart disease, for example, are also thought to improve mood and help depression. The group is now planning additional studies to confirm whether inflammation is a common link between chronic physical and mental illness.
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Social stress-triggered increase of interleukin-6 in the brain exacerbates an animal model of multiple sclerosis. (2007) www.sciencedaily.com
From the article:
To create a stressful environment, researchers housed three young male mice together for several weeks. After the mice established a stable social hierarchy, researchers introduced an older aggressive male into the residence for a couple of hours. The intruder exhibits aggressive behavior – posturing, fighting, wounding, pursuit – that results in submissive behaviors and social defeat in the younger resident mice. This procedure was repeated for three consecutive nightly two-hour sessions with one night off, followed by an additional three nightly sessions. To keep the mice from getting used to the intruder, a new intruder was introduced for each session.
What they found was this stress appears to elevate levels of IL-6, which subsequently increases the severity of the MS-like illness. Furthermore, using specific IL-6 neutralizing antibody treatments during the stress exposure can prevent the stress-related worsening of the disease, said the authors.
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Furthermore, interventions that prevented or reversed the stress-induced increases in IL-6 in the mouse model may have implications for humans, said Meagher. It is possible that the adverse effects of social conflict on people who are vulnerable to certain inflammatory diseases may be prevented or reversed by treatments aimed at blocking increases in this cytokine. Recent evidence suggests that some potential interventions include certain anti-inflammatory drugs, exercise, antidepressant medication, omega-3 fatty acids, and mindfulness relaxation training. However, human clinical trials are needed to fully evaluate this issue.
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Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010) www.sciencedaily.com
From the article:
Activation of the immune system caused mice to learn to run less on wheels in their cages – an activity they normally like. The mice resumed their normal activity when the action of interleukin-6, an immune hormone that carries “sickness” signals to the brain, was blocked.
“Our findings suggest that blocking the action of interleukin-6 might reduce depression symptoms, like fatigue or loss of interest in pleasurable activities, in people who are depressed and who have elevated levels of interleukin-6,” said Simon Sydserff, PhD, a senior research scientist at BrainCells Inc., who conducted the research while with AstraZeneca Pharmaceuticals.
Scientists previously observed that some people became depressed due to an immune response to illness or stress. Elevated levels of immune hormones like interleukin-6 have been found in some depressed patients who are otherwise healthy.
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Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013) www.sciencedaily.com
Psychosocial stress promotes the release of IL-6, potentially driving the development of depression.
Psychosocial stress, such as that experienced with divorce, discrimination, trauma, or the death of a child, can have profound effects on the human body. For example, evidence indicates that stress alters the immune system, driving inflammatory processes and impairing antiviral responses. Findings from a 2013 study suggest that psychosocial stress promotes the release of interleukin 6 (IL-6), potentially driving the development of depression.
IL-6 is a pro-inflammatory cytokine that plays an important role as a mediator of fever and the body’s immune response. It is produced by almost all immune cells and is induced in the context of infection, autoimmunity, or cancer. Many physiological processes are influenced by IL-6, including glucose metabolism, blood cell production, neuroendocrine regulation, and fatigue, among others. IL-6 levels are often elevated in people who have depression.
The investigators conducted their study using mice that had undergone radiation to destroy their bone marrow, compromising their immune function. Then they transplanted bone marrow from mice that exhibited either high or low levels of IL-6 levels in response to stress into the immune-compromised animals. Then they exposed the animals to a social stressor.
They found that mice that received transplants from those that exhibited high IL-6 levels in response to stress demonstrated more depression-like behaviors than the mice that received transplants from those that exhibited low IL-6 levels. These findings suggest that IL-6 promotes a pro-inflammatory state that promotes depression-like symptoms in response to psychosocial stress. Identifying therapeutic strategies that inhibit IL-6 may benefit people who are vulnerable to the effects of psychosocial stress.
Interestingly, hyperthermia, such as that experienced with sauna use or hot baths, has been shown to reduce IL-6 levels. Learn more about the beneficial effects of sauna use in our overview article.
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Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021) www.sciencedaily.com
Microglia and IL-6 drive the negative mood often associated with inflammation.
People who have certain neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, or stroke, often exhibit low mood. Evidence suggests that inflammation plays a role in the pathogenesis of these neurological disorders and likely influences mood, as well. Findings from a 2021 study suggest that microglia activation drives the low mood often associated with neurological disorders.
Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.
The investigators used chemogenetics, a research technique that uses drugs or other chemicals to modulate neural activity, to stimulate microglia activation in the brains of mice. They noted that levels of interleukin-6 (IL-6, a pro-inflammatory cytokine) and prostaglandins (hormone-like molecules that are involved in inflammation) increased in the animals' brains. In addition, the animals exhibited a low mood. Blocking microglia activity restored the animals' positive mood, however.
These findings suggest that microglia drive the low mood often associated with inflammation and that IL-6 is a prominent player in this process. Learn more about the role of inflammation and mood in this episode featuring Dr. Charles Raison.
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Mouse study suggests that interleukin-6 (IL-6) may regulate body weight by increasing substances in the brain that trigger weight loss. (2012) www.sciencedaily.com
From the article:
The results show that the cells that are affected by interleukin-6 produce substances that not only affect our sense of hunger and fullness but also control the body’s ability to burn fat. “Interleukin-6 increases levels of substances in the brain that trigger weight loss, which could explain why high levels of this molecule lead to weight loss,” says doctoral student Erik Schéle, who is presenting the results in his thesis.
It is known that our normally low levels of interleukin-6 in the brain increase dramatically during an infection, typically accompanied by reduced hunger and fatigue.
“Our previous findings would indicate that interleukin-6 can play a key role in regulating the metabolism of healthy individuals too,” says Erik Schéle.
“This is clearly substantiated by our finding that mice which lack interleukin-6 get fat, and that the metabolism of rats injected with interleukin-6 directly into the brain increases.”
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In a mendelian randomization study, genetically predicted levels of interleukin 6 (IL-6) were associated with neuropsychiatric disorders. www.sciencedaily.com
IL-6 may drive inflammation in neuropsychiatric disorders.
Neuropsychiatric disorders are the leading cause of disability among people living in the United States, accounting for nearly 20 percent of all years of life lost to disability and premature death. Evidence suggests that brain inflammation is a key player in neuropsychiatric disorders, the effects of which may be bidirectional. A recent study identified potential links between inflammation and structural alterations in regions of the brain implicated in neuropsychiatric disorders.
The brains of people with neuropsychiatric disorders exhibit a range of abnormal structural alterations, but researchers don’t fully understand what drives these abnormalities. One possible player is interleukin-6 (IL-6), a cytokine that can cross the blood-brain barrier, increasing the barrier’s permeability and promoting brain inflammation. In turn, this inflammation can impair synaptic pruning, a natural process that occurs in the brain between early childhood and adulthood and eliminates extra synapses. Inappropriate synaptic pruning is associated with some neuropsychiatric disorders, including schizophrenia and autism.
The investigators searched for evidence of potential causality in the association between inflammatory cytokines and altered brain structure using Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Using data from more than 20,000 adults enrolled in the UK Biobank study, the researchers looked for associations between genetic variants that influence levels of interleukin-6 (IL-6, a pro-inflammatory cytokine), as well as other inflammatory factors. and changes in gray matter volume in specific areas of the brain. They also examined postmortem brain tissue to assess gene expression in the brain areas of interest.
They found that genes that influence the production of pro-inflammatory molecules, especially IL-6, are strongly linked with brain structure in the temporal and frontal regions of the brain, areas of the brain commonly implicated in neuropsychiatric disorders. The postmortem analyses revealed that the overproduction of these pro-inflammatory genes is associated with disorders such as epilepsy, cognitive disorder, schizophrenia, psychotic disorder, and autism spectrum disorder.
These findings suggest that pro-inflammatory pathways, especially those associated with IL-6, are essential for normal brain structural development and IL-6 elevation may drive structural alterations implicated in neuropsychiatric disorders. Evidence suggests that heat stress reduces symptoms associated with depression, a type of neuropsychiatric disorder. Learn about a clinical trial that is investigating the benefits of heat stress in this episode featuring Dr. Ashley Mason.
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Interleukin-6 (IL-6) may have a neuroprotective function, mouse study suggests. (2003) www.sciencedaily.com
From the article:
One of the biggest challenges we face as a society is the eventual loss and degeneration of neurons from many causes, including many diseases – from Alzheimer’s disease to multiple sclerosis to Parkinson’s disease – and other sorts of injury.
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To function in a cell, IL-6 has to bind in a specific place – called a “receptor site” – in a specific way. Dr. Rodriguez and colleagues were intrigued that IL-6 uses the same receptor site used by compounds whose job is to promote neuronal survival. “To me, that was pretty wild,” Dr. Rodriguez says. “So I hypothesized that maybe this IL-6 is also playing a role in protecting neurons.”
Testing this idea required extensive genetic work to produce different mouse groups that varied in their ability to produce IL-6. All were infected with a virus that causes a degenerative nerve disease. Animals with the IL-6 gene got mildly sick, but did not die. Mice lacking the IL-6 gene got severely sick and started dying. Why?
To find a cause of death, the Mayo Clinic team analyzed the animals' tissues. Their findings: neurons in the spinal cords of mice lacking IL-6 were degenerating dramatically. This evidence supported their hypothesis of a neuron-protection role for IL-6. It also led them to their next question: Where is IL-6 made?
An analysis of the brains of healthy mice possessing the IL-6 gene surprised them. “You look for IL-6 in the brain of a normal, healthy animal, and there is no IL-6 in a normal healthy animal!” Dr. Rodriguez says. “So then we infected the animals with the virus. Now when we looked for IL-6, guess what? It was everywhere.”
Specifically, IL-6 was found in astrocytes.
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Low levels of interleukin-6 (IL-6) in the prefrontal cortex enhanced reversal learning in rats. (2014) www.sciencedaily.com
Cytokine signaling in the brain promotes cognitive flexibility.
Cytokines are small signaling proteins that play essential roles in the body’s inflammatory process. They are produced primarily by immune cells, but they are also produced at basal levels in the brain, where they participate in memory and learning. Findings from a 2014 study suggest that cytokine signaling in the brain is necessary for reversal learning.
Reversal learning is a form of cognitive flexibility. It allows an organism to determine that a reward for a particular activity has changed and then adjust its behavior accordingly. Reversal learning enables an organism to disengage from ongoing behavior, a quality that is related to impulsive or compulsive actions. Evidence suggests that reversal learning is impaired in neuropsychiatric disorders such as depression, schizophrenia, and obsessive-compulsive disorder.
The researchers conducted a three-part experiment. First, they blocked the production of interleukin-6 (IL-6), a type of cytokine, in the brains of rats. They subjected one-half of the rats to cold stress (which has been shown to impair reversal learning), and the other half was left in a non-stressful environment. Then they tested both the stressed and non-stressed animals' reversal learning capacities. Surprisingly, they found that blocking IL-6 impaired reversal learning in both groups of animals, suggesting that basal IL-6 activity in the brain (in the absence of stress or inflammation) may aid learning.
In their second experiment, the researchers determined that IL-6 is produced in the orbitofrontal cortex, a region of the brain responsible for decision-making and learning. They also determined that the mechanism by which IL-6 facilitates reversal learning was a signaling pathway called JAK/STAT, which is involved in multiple physiological processes.
Finally, they restored IL-6 levels in the orbitofrontal cortex region of the animals' brains. They subjected them to cold stress again and re-tested their reversal learning capacities. They found that restoring IL-6 to the animals' brains attenuated the stress-induced reversal learning losses.
These findings suggest that a basal level of the cytokine IL-6 is essential for reversal learning in rats. The researchers posited that although IL-6 is typically a pro-inflammatory cytokine, it may exert differential effects under different conditions. For example, it may promote learning deficits under inflammatory conditions, but facilitate learning under basal (non-stressed, non-inflammatory) conditions.
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Obese when compared to those with normal body fat had much higher inflammation: 53% higher CRP, 30% higher TNF-a, 17% higher WBC count, 42% higher IL6 linkinghub.elsevier.com
Strong link between accumulated visceral fat and chronic inflammation.
A person’s waist-to-hip ratio compares their waist measurement to that of their hips. A high ratio can be an indicator of excess fat accumulation around the waist, often referred to as visceral fat. Findings from a 2005 study suggest that visceral fat is associated with markers of inflammation.
Visceral fat is stored in the abdominal cavity near the liver, pancreas, and intestines. The accumulation of visceral fat is linked to increased risk of cardiovascular disease and other chronic diseases. Many factors drive visceral fat accumulation, including poor sleep, an obesogenic diet, and sugar-sweetened beverage intake, among others.
The study involved more than 3,000 healthy males and females (18 to 89 years old) living in Greece. The investigators calculated the participants' body mass index (BMI) and measured their waist and hip circumferences. Participants provided blood samples for the assessment of inflammatory biomarkers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), amyloid A (an apolipoprotein secreted in the acute stage of inflammation), white blood cells, and interleukin-6 (IL-6).
The investigators found that approximately 36 percent of the males and 43 percent of the females had excess visceral fat. Approximately 20 percent of the males and 15 percent of the females had obesity. Participants with greater visceral fat had 53 percent higher CRP, 30 percent higher TNF-alpha), 26 percent amyloid A, 17 percent higher white blood cell counts, and 42 percent higher IL-6, compared to participants with normal fat distribution. The relationship between visceral fat and inflammatory markers was stronger than that between obesity and inflammation, even when considering the participants' age, income, education, and other potential confounding factors.
These findings suggest that visceral fat and inflammatory processes are linked. The investigators posited that excess accumulation of visceral fat may increase the risk for cardiovascular disease by driving inflammation.
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Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function www.frontiersin.org
Surgery and anesthesia may contribute to cognitive impairment.
Anesthesia, a medical treatment that involves the use of anesthetic drugs, is a widely accepted strategy for managing pain during surgery. Evidence suggests that mice that have undergone surgery that involved anesthetic treatment exhibited signs of postoperative cognitive impairment. Findings from a 2017 study suggest that surgery in combination with the anesthetic drug isoflurane induces blood-brain barrier dysfunction, contributing to cognitive impairment.
Anesthetic drugs can be administered orally, intravenously, or via inhalation. Isoflurane is one of the most common inhaled anesthetics used in humans. Scientists don’t fully understand the mechanisms by which inhaled anesthetics work, but they appear to affect the central nervous system by depressing neurotransmission pathways. Previous research has shown that isoflurane increases several markers of inflammation.
The investigators wanted to determine whether the effects of surgery and anesthesia on blood-brain barrier permeability and cognitive function were related to age and/or the action of interleukin-6 (IL-6), a proinflammatory molecule. The experiment involved three types of mice: young female mice, old female mice, and young female mice that don’t carry the gene for IL-6. Previous research has shown that female mice are more vulnerable to the cognitive impairment associated with surgery and anesthesia. Half of the mice underwent a simple surgical procedure under anesthesia (isoflurane), while the remaining half did not. After the mice that had had surgery recovered, the investigators assessed all the animals' cognitive performance via a maze test, measured IL-6 in the animals' blood, and quantified proteins involved in maintaining blood-brain barrier integrity in the animals' brains.
They found that the mice that underwent anesthesia and surgery had greater blood-brain permeability and higher IL-6 levels than those that did not undergo the procedures. Notably, permeability increased as IL-6 levels and age increased. Levels of proteins involved in maintaining blood-brain barrier integrity were lower in the mice that underwent the procedure, and older mice were more likely to experience cognitive deficits after the procedures than younger mice.
These findings suggest that surgery with anesthesia induces cognitive decline in an age-dependent manner, and this decline may be due to inflammatory processes that drive blood-brain barrier dysfunction. Learn more about the blood-brain barrier in our new overview article.
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Cereal fiber is associated with a lower risk of cardiovascular disease. www.sciencedaily.com
Fiber from cereal grains reduces cardiovascular disease risk.
Cardiovascular disease is the second leading cause of death worldwide. However, much of the risk associated with cardiovascular disease is modifiable via lifestyle, such as exercising, eating a healthy diet, and not smoking. Findings from a recent study suggest that eating foods rich in dietary fiber, especially the fiber present in cereal grains, reduces the risk of cardiovascular disease.
Dietary fiber is a broad term that refers to the non-digestible components of plant-based foods. It is generally characterized by its solubility in water, viscosity (i.e., ability to form thick gels), and fermentability. Cereal grains contain a mixture of insoluble fibers that bulk stool, viscous fibers that slow digestion, and fermentable fibers that feed the gut microbiota. Gut microbes break down cereal fiber, releasing micronutrients trapped in the fiber matrix and producing beneficial metabolic byproducts, such as short-chain fatty acids. Compared to fruit and vegetable fibers, cereal grain fibers tend to reduce the glycemic effect of meals and improve blood lipids, while supporting a healthy and diverse microbiota.
The investigation involved more than 4,100 participants (aged 65 years and older) enrolled in the Cardiovascular Health Study. Participants provided detailed information about their demographics, dietary intake, and medical history, including cardiovascular events. Because evidence indicates that cereal fibers reduce markers of inflammation, including C-reactive protein, the investigators measured various inflammatory markers, including CRP, IL-6, CD14, CD163, IL-2 receptor α, IL-1RA, IL-18, and TNF receptor 1, in the participants' blood.
The investigators found that higher cereal grain fiber intake markedly reduced cardiovascular disease risk and lowered the inflammatory markers CRP, IL-6, and IL-1RA. However, statistical analysis revealed that this decrease in inflammation had a modest effect on reducing cardiovascular risk, mediating just one-sixth of the association between cardiovascular disease and cereal grain fiber intake.
These findings suggest that eating foods rich in cereal grain fibers reduces the risk of cardiovascular disease and lowers inflammation. Additional studies are needed to tease out all the mechanisms that drive the protective effects of cereal fiber on cardiovascular health.
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Aerobic exercise (wheel running) prevents cancer tumor formation, growth, and cachexia (cancer weight loss) in mice www.sciencedaily.com
Effect of aerobic exercise on cancer in mice:
Training mice regularly on a wheel (the mouse version of a treadmill) decreased the growth of multiple types of tumors, including skin, liver, and lung cancers. Furthermore, mice that exercised regularly had a smaller chance of developing cancer in the first place. The beneficial effects of running went beyond tumor formation and growth, extending to cancer-associated weight loss, a process termed cachexia that is seen in cancer patients. Mice that exercised regularly showed no signs of cancer-associated weight loss in the researchers' lung cancer mouse model.
Myokine signaling from the muscles:
The researchers say that, the production of adrenaline results in a mobilization of immune cells, specifically one type of immune cell called a Natural Killer (NK) cell, to patrol the body. These NK cells are recruited to the site of the tumor by the protein IL-6, secreted by active muscles. The NK cells can then infiltrate the tumor, slowing or completely preventing its growth. Importantly, the researchers note that injecting the mice with either adrenaline or IL-6 without the exercise proved insufficient to inhibit cancer development, underlining the importance of the effects derived only from regular exercise in the mice.
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Muscle produces tumor-suppressing compounds during exercise in men with prostate cancer. www.ecu.edu.au
Exercise oncology is an emerging branch of medicine that studies the application of exercise medicine in the treatment of cancer. Although there is a strong base of epidemiological research that supports a relationship between increased physical activity and decreased cancer severity and death, the molecular mechanisms that underlie this relationship require further research. Findings of a recent report identify myokines that suppress tumor growth in patients with prostate cancer.
Myokines are molecules released from muscle cells that signal to non-muscle tissues that the body is physically active. Studies in non-human animals have shown that myokines such as oncostatin M, decorin,, and interleukin (IL)-6 suppress cancer growth; however research in humans is lacking.
The investigators recruited 10 men (average age, 73 years) with prostate cancer who were undertaking androgen deprivation therapy, which includes drugs that block the action of testosterone and other male hormones. Participants completed 12 weeks of exercise training that included three sessions-per-week of supervised resistance training and daily self-directed moderate-to-vigorous physical activity. The investigators measured the participants' muscle strength, body composition, and serum myokine concentration before and after the exercise training intervention. They also grew prostate cancer cells in vitro, exposed them to serum from participants taken before and after exercise training, and observed the effects on cancer cells directly.
Participants lost about six pounds of fat and eight pounds of total body weight during the intervention period. Participants significantly increased their strength, measured during the leg press (57 pound increase) and chest press (16 pound increase). Serum concentrations of oncostatin M increased by 82 percent while other myokines did not increase or could not be measured. Finally, prostate cancer cells incubated with serum taken post-exercise training reduced cancer growth by 22 percent compared to serum taken prior to exercise training.
These results show that exercise induced the expression of myokines with tumor-suppressing ability in patients with prostate cancer. Future research is needed to refine the prescription of intensity, frequency, and type of exercise in cancer treatment.
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Co-supplementation with magnesium and vitamin D aids weight loss, improves mood, and reduces systemic inflammation. pubmed.ncbi.nlm.nih.gov
For decades, deficiencies in micronutrients such as magnesium and vitamin D have been linked to conditions such as depression and obesity, as well as their associated hallmarks of systemic inflammation. These observations raise questions about whether certain nutritional inadequacies might play a causal role in these conditions and whether supplementation may help regulate symptom severity. Now, a recent randomized double-blind placebo-controlled clinical trial reveals that co-supplementation with magnesium and vitamin D significantly decreases depression scores and body weight in healthy women with obesity.
The study recruited 102 women with obesity (body mass index, 30–40; ages, 20-45 years) with mild-to-moderate depression and no indication of other health issues such as hormonal dysfunction, autoimmune disease, or diabetes. The study investigators randomly allocated the women to one of four groups to receive varying combinations of a weekly soft gel containing 50,000 international units (IU) of vitamin D, a daily tablet of 250 milligrams magnesium, and/or a placebo. The groups comprised:
1) Co-supplementation: weekly vitamin D + daily magnesium
2) Vitamin D only: weekly vitamin D + daily magnesium placebo
3) Magnesium only: daily magnesium + weekly vitamin D placebo
4) Control: weekly vitamin D placebo + daily magnesium placebo
The investigators collected participants’ blood samples at baseline and following eight weeks of supplementation. The samples revealed that while the women on average had adequate baseline serum levels of magnesium and borderline-adequate levels of vitamin D, their health outcomes and biomarkers nonetheless showed the greatest improvements as a result of co-supplementation with both micronutrients. For instance, women who received both magnesium and vitamin D lost more weight over the duration of the intervention compared to all the other groups, in the absence of any observed changes in their dietary patterns. They also showed the greatest average reduction in depression scores over time, although all participants (including controls) exhibited some degree of symptom relief after the eight-week intervention - an observation the researchers attributed in part to the placebo effect.
The women’s blood samples revealed a similar picture, with co-supplementation outperforming all other conditions (although individual supplementation with either vitamin D or magnesium still yielded significant improvements over controls). For instance, combining magnesium and vitamin D achieved the greatest reduction in plasma levels of pro-inflammatory tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6). It also generated the highest boost in brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT1) – a protein widely known for its involvement in regulating autophagy and longevity-promoting genes.
These findings reveal that co-supplementation with a weekly 50,000 IU dose of vitamin D and a daily 250 mg of magnesium can aid weight loss, enhance mood, and improve a host of blood biomarkers pertaining to systemic inflammation, brain functioning, and longevity. Moreover, the fact that positive health outcomes can be observed despite an absence of marked micronutrient deficiencies raises the possibility that current medical guidelines on adequate ranges of plasma levels and RDAs for vitamin D and magnesium, respectively, may be insufficiently high for optimal health outcomes.
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Fermented foods decrease inflammation and increase diversity of the gut microbiota. www.sciencedaily.com
The gut microbiota is composed of the community of bacteria, archaea, fungi, and viruses that live in the human intestine. Dietary components influence the composition and activity of the microbiota. For example, foods high in dietary fiber, such as whole grains and beans, and fermented foods, such as yogurt and sauerkraut, support an abundant and diverse gut microbiota, which is associated with lower disease risk. Authors of a report released this week investigated the effects of high-fiber and fermented foods on the gut microbiota and immune system.
The authors recruited 36 healthy adult participants (average age, 52 years) who consumed little dietary fiber (fewer than 20 grams of fiber per day) and only one serving of fermented foods or less per day. They instructed half of the participants to add 20 grams or more of fiber per day to their baseline consumption. They instructed the other half of participants to consume six servings or more of fermented foods per day. Participants in both groups consumed their assigned diets for 10 weeks and recorded their food and beverage intake to assess adherence to study instructions. Participants also provided blood samples for the assessment of inflammation and fecal samples for the characterization of the gut microbiome at numerous time points throughout the study.
A high-fiber diet did not reduce inflammation, but did alter the composition of the microbiota, increasing the abundance of bacteria known to metabolize dietary fibers, such as the genus Lachnospira. Higher fiber consumption also promoted greater secretion of enzymes associated with fiber metabolism and increased abundance of fiber metabolites, such as short chain fatty acids. A high-fermented food diet steadily increased microbiota diversity over time and decreased multiple markers of inflammation, including interleukin (IL)-6, IL-10, and IL-12b, among others.
These results suggest that probiotics from fermented foods increase microbiota diversity and decrease inflammation. The authors noted that the lack of immunological response in participants consuming the high fiber diet may have been due to the short duration of the intervention.
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Greater muscle strength reduces depression risk. www.psypost.org
Depression is characterized by mood alterations, such as increased sadness and irritability, and physiological changes, such as decreased sleep, appetite, and sexual desire. Previous research has reported a relationship between increased muscle strength and lower depression risk in older adults. Findings of a recent study detail the relationship between muscle strength and depression risk in young adults.
Cytokines are proteins that participate in cell-signaling. Pro-inflammatory cytokines are increased in depression and contribute to the dysfunction of neurotransmission, hippocampal neurogenesis, and stress-related nervous system activation. Skeletal muscle cells secrete a number of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-15. A previous study demonstrated a relationship between lower levels of inflammation in adolescents with increased muscle strength and decreased body fat, but the study did not measure depression risk.
The authors included 600 female participants without depression (average age, 19 years) in their analysis who were part of a larger observational study of physical fitness and health in Chinese college students. Participants completed a survey to measure depression symptoms and a physical exam including the use of a dynamometer to measure grip strength, a proxy for total skeletal muscle strength. The authors collected these measures at baseline and at a one-year follow-up. They classified participants into one of four categories based on the amount of grip strength they gained over the one-year study period.
At the one-year time point, about 11 percent of participants reported depressive symptoms. Participants who gained the most grip strength over the one-year study period had a 66 percent lower risk of depression compared to participants who gained the least grip strength. Participants with the greatest gains in grip strength tended to be younger and smoke less at baseline than participants with the least gains in grip strength. Finally, gains in grip strength were significantly related to body mass index (BMI) at baseline. Underweight, defined as a BMI less than 18.5, was more common in participants with the lowest gains in grip strength (43 percent), while overweight, defined as a BMI greater than 25, was more common in participants with the greatest gains in grip strength (23 percent).
The authors concluded that increased grip strength is associated with a lower risk of depressive symptoms in young adults.
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Omega-3 fatty acids reduce symptoms of depression. www.kcl.ac.uk
Depression – a mood disorder that affects 322 million people worldwide – is characterized by profound sadness, anxiety, and physical complaints. People who have depression often have higher levels of systemic inflammation (which can affect brain health) compared to those without depression. Findings from a new study suggest that omega-3 fatty acids reduce symptoms of depression through their anti-inflammatory effects on the brain.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 fatty acids derived primarily from fish. They exert a wide range of beneficial effects on the human body. Evidence from a clinical trial indicates that omega-3 fatty acids reduce symptoms of depression associated with inflammation.
Chronic inflammation plays key roles in the development of many diseases, including cancer, cardiovascular disease, and diabetes. Inflammation in the brain impairs neurogenesis, the process of forming new neurons. Impaired neurogenesis negatively influences mood and cognitive function.
The authors of the study conducted two experiments. In the first experiment, they pre-treated human hippocampal cells with either EPA or DHA and then exposed the cells to interleukin (IL)-1 beta, IL-6, and interferon-alpha – proteins that drive chronic inflammation. They found that EPA and DHA maintained neurogenesis and prevented programmed cell death via the effects of lipid mediators – a class of omega-3 fatty acid byproducts that influence immune health and inflammation.
In the second experiment, the authors gave 22 people who had been diagnosed with depression either 3 grams of EPA or 1.4 grams of DHA for 12 weeks. They measured lipid mediators in the participants' blood and assessed their depression symptoms. The authors found that the anti-inflammatory lipid mediators increased in the participants' blood. They also noted that the participants' depressive symptoms decreased approximately 64 percent with EPA and 71 percent with DHA.
These findings suggest that omega-3 fatty acids reduce the inflammation associated with depression and improve depressive symptoms. This was a very small study, however, and did not include a control group. Further research is needed to confirm these findings. Learn more about the role of inflammation in depression in this clip featuring Dr. Charles Raison.
For a quick and tasty way to get more omega-3 fatty acids into your diet, check out this recipe video featuring Dr. Rhonda Patrick.
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Daily apple consumption decreases multiple markers of obesity-associated inflammation. academic.oup.com
Obesity is characterized by chronic low-grade inflammation, which contributes to the development of cardiovascular disease. While processed foods and beverages high in saturated fats and simple sugars are associated with a higher risk of cardiovascular disease, diets rich in plant-based foods, including fruits, are associated with a lower risk. Findings of a recent report detail the effects of daily apple consumption on inflammation, endotoxemia, and metabolism.
Causes of obesity-associated inflammation include leaky gut, a condition where the intestinal barrier is compromised, leading to increased levels of bacterial endotoxin (toxins that are released when bacteria die) in the bloodstream (called endotoxemia). This increase in endotoxin levels activates white blood cells to secrete pro-inflammatory cytokines such as interleukin (IL)-6 and IL-17. Plant foods such as apples are beneficial for people with obesity because they are rich in bioactive compounds that decrease inflammation and dietary fibers that strengthen the gut barrier.
The researchers recruited 46 participants with overweight and obesity and directed them to avoid foods and beverages rich in polyphenols and/or dietary fibers (e.g., coffee, vegetables, grains, beans, and red/purple/blue fruits) for two weeks. Next, they assigned half of the participants to consume three Gala apples per day for six weeks or to avoid apples. Both groups continued to eat a diet with limited polyphenols and dietary fibers. Participants provided blood samples for the collection of white blood cells and measurement of pro-inflammatory cytokines. After isolating the white blood cells, the researchers stimulated them with endotoxin and measured their response.
Apple consumption decreased plasma C-reactive protein (a pro-inflammatory cytokine) by 17 percent, IL-6 by 12 percent, and endotoxin-binding protein by 20 percent compared with no apple consumption. White blood cells from participants who consumed apples secreted 28 percent less IL-6 and 11 percent less IL-17. While apple consumption increased total antioxidant capacity in blood by 10 percent, it had no effect on cardiovascular disease markers.
These findings suggest that six weeks of daily Gala apple consumption helped mitigate inflammation in those consuming a diet low in polyphenols and fiber, a common feature of the Western diet pattern. Apple consumption may decrease cardiovascular disease risk in those with obesity, even without weight loss.
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Omega-3 supplementation reduces inflammation and cellular aging in response to social stress. www.nature.com
Omega-3 fatty acid consumption reduces the risk of death from cardiovascular disease and all causes. By reducing inflammation, lengthening telomeres, and blunting the body’s response to stress, omega-3 fatty acids lessen the effects of aging on a cellular level. Authors of a recent study tested the effects of omega-3 supplementation on inflammation and telomere length in response to stress.
Telomeres are often compared to the plastic tips on the end of shoelaces (aiglets) because telomeres protect chromosomes from fraying on the ends. Both acute and chronic stress increase inflammation, which can cause chromosomes to become frayed when telomeres are short. Once chromosomes lose their telomeres, their DNA cannot be replicated, and this accelerates aging.
The randomized, controlled intervention trial included 138 sedentary, adults with overweight between the ages of 40 and 85 years. The participants received daily supplements providing 2.5 grams of omega-3s, 1.25 grams of omega-3s, or a placebo for four months. Before and after the intervention, the participants took the Trier Social Stress Test, a testing platform in which a person must deliver a speech and perform mental arithmetic in front of an audience. Participants also provided blood and saliva samples as a means to measure cortisol (a stress hormone), telomerase (an enzyme that helps maintain telomere length); anti-inflammatory cytokines, including interleukin (IL)-10 (IL-10); and pro-inflammatory cytokines, including IL-6, IL-12, and tumor necrosis factor-alpha (TNF-alpha).
Following the stress test, participants in the placebo group experienced a 24 percent reduction in telomerase activity and a 26 reduction in IL-10; however, both omega-3 groups were protected from this response. This relationship was statistically significant and accounted for baseline stress reactivity, age, waist circumference, and sex. Participants who received 2.5 grams of omega-3s had a 19 percent reduction in cortisol levels and a 33 percent reduction in IL-6 compared to the placebo group.
The authors concluded that by reducing inflammation and stress hormone levels, omega-3 supplementation may boost cellular repair and slow aging. This decrease in stress response may also translate to reduced risk of depression, making these findings relevant to mental health as well.
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Treatment with interferon-α2b speeds up recovery of COVID-19 patients in exploratory study www.eurekalert.org
From the article:
“Interferons are our first line of defence against any and all viruses - but viruses such as corona-viruses have co-evolved to very specifically block an interferon response … Treatment with interferon will override the inhibitory effects of the virus.”
Fish says that the research team considered IFN-α therapy for COVID-19 after they demonstrated interferons had therapeutic benefits during the SARS outbreak of 2002 and 2003.
In this study, the authors examined the course of disease in a cohort of 77 individuals with confirmed COVID-19 admitted to Union Hospital, Tongii Medical College, Wuhan, China, between January 16th and February 20th 2020. The individuals evaluated in this study consisted of only moderate cases of COVID-19, as none of the patients required intensive care or oxygen supple-mentation or intubation. The researchers demonstrated a significantly different rate of viral clearance for each treatment group and notably, IFN-α2b treatment accelerated viral clearance by approximately 7 days. Treatment with IFN-α2b, whether alone or in combination with ARB, accelerated viral clearance when compared to ARB treatment alone. IFN treatment was also demonstrated to significantly reduce circulating levels of IL-6 and CRP, whether alone or in combination with ARB.
Despite the study’s limitations of a small, non-randomised cohort, the work provides several important and novel insights into COVID-19 disease, notably that treatment with IFN-α2b accelerated viral clearance from the upper respiratory tract and also reduced circulating inflammatory biomarkers, hinting at functional connections between viral infection and host end-organ damage by limiting the subsequent inflammatory response in the lungs of patients.
As an uncontrolled, exploratory study, Fish says a randomized clinical trial is a crucial next step: “A clinical trial with a larger cohort of infected patients that are randomized to treatment with interferon-alpha or to a placebo would further this research”.
In the meantime, the findings from this study are the first to suggest therapeutic efficacy of IFN-α2b as an available antiviral intervention for COVID-19, which may also benefit public health measures by shortening the duration of viral clearance and therefore slowing the tide of the pandemic."
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Exercise causes acute elevation of IL-6 which reduces postprandial blood glucose levels and insulin secretion by delaying gastric emptying in men with type 2 diabetes.
IL-6 is a cytokine with both negative and positive effects. Chronic elevation of IL-6 reflects ongoing inflammation and is linked to type 2 diabetes and atherosclerosis. In contrast, acute elevation of IL-6 from exercise inhibits inflammatory cytokines and stimulates the production of anti-inflammatory cytokines in humans.
To learn more about the role of exercise-induced IL-6, the postprandial inflammatory response and their effects on the brain…check out my interview with Dr. Charles Raison. This episode has a timeline, transcript, summary, and glossary to help find and understand the talking points.
Charles Raison, MD podcast: https://www.foundmyfitness.com/episodes/charles-raison