Interleukin-6 (IL-6) mediates delirium-like phenotypes in a mouse model of urinary tract infection. (2021)
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.
Enjoying this research? Get deeper insights like this delivered every other week.
Every other week our Premium Members receive deep dives like this alongside Rhonda's commentary and 8+ other hand-picked papers.
“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.