Researchers in the departments of Neurology, Neurosurgery, Psychiatry, Medicine and Biomedical Sciences at Cedars-Sinai have shown that an immunosuppressive drug similar to the one used to treat COVID-19 reversed symptoms of delirium in mice whose lungs were injure during a mechanical process. respiratory assistance Their study, published in the peer-reviewed journal Critical Care, could pave the way for clinical trials of immune system inhibitor therapy for ventilator-induced delirium in patients.
Delirium, a serious condition that causes confusion and reduced awareness of a person’s surroundings, develops in more than 70 percent of mechanically ventilated patients, said Shouri Lahiri, MD, director of the Care Unit Review of Neuroscience and Neurocritical Care Research at Cedars-Sinai. and lead author of the study.
“Delirium is an important clinical problem, but we have very limited tools to treat it,” Lahiri said. “This work in mice gives us insight into the biology of the disease and, for the first time, offers us an avenue to directly test potential treatments.”
Ventilator-induced delirium is common and may be unavoidable in patients with severe lung damage or disease, including severe cases of COVID-19. This is because injury to lung tissue causes inflammatory proteins to travel through the blood to the brain, resulting in confusion and disorientation.
“These inflammatory proteins help regulate the body’s response to injury and infection, and here we show that by blocking these proteins in the blood, we disrupt their pathway to the brain and reverse the delirium that patients experience,” Lahiri said.
In the study, Lahiri and his team administered a monoclonal antibody that blocks the function of the IL-6 receptor, which is similar to an immunosuppressant drug called tocilizumab that is given to patients with severe COVID-19, to injured mice ventilator-induced pulmonary They observed changes in the mice’s brains, and also signs of delirium in their behavior in specially designed mazes.
“We showed that when we inhibited the immune response in these mice, their brain changes associated with delirium and their behavior improved,” Lahiri said. “This is important because we link brain changes to behavior.”
In previous work, Lahiri and his team also established a connection in mice between the immune response and delirium associated with urinary tract infection.
These collective findings illuminate brain changes associated with delirium symptoms in critically ill patients. They also make clear the need for further investigation into the important role of immunosuppressive therapy as a treatment for the debilitating delirium that so commonly follows ventilator use and common infections such as urinary tract infections.”
Nancy L. Sicotte, MD, Chair of the Department of Neurology and Women in Neurology Distinguished Chair
Lahiri said future studies will investigate whether immunosuppressive therapy, in addition to reversing short-term delirium, could have long-term benefits.
“It is well known that delirium could have long-term benefits associated with long-term cognitive impairment and accelerate long-term cognitive decline,” Lahiri said. “And we know that by mitigating delirium, we’re likely to have an effect on long-term cognitive decline. The inflammatory response associated with COVID-19 also leaves an imprint on the brain that persists, so I think these immunomodulatory therapies can also help improve the long COVID”.
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Journal reference:
Anwar, F. et al. (2022) Systemic inhibition of interleukin-6 ameliorates acute neuropsychiatric phenotypes in a murine model of acute lung injury. Critical Care. doi.org/10.1186/s13054-022-04159-x.