Intensive care units can be dangerous places for patients. In addition to the causes that led them to the ICU, some patients develop a dangerous inflammation that can quickly spread throughout their body. Systemic inflammatory response syndrome (SIRS) claims as many as 200,000 American lives each year.

Some of the cases are triggered by a known infection, but others remain something of a mystery.

Miller School of Medicine researchers have clearly identified, for the first time, how the brain modulates the inflammatory response in SIRS, the tenth leading cause of death in intensive care units. Their study, published in April in the Proceedings of the National Academy of Sciences, identified eight genes that play a role inside the brain in triggering SIRS.

“It has never been this clear that the brain is an important site of regulation of this inflammatory response,” says Ma-Li Wong, M.D., professor and vice chair for translational research in the Department of Psychiatry and Behavioral Sciences at the Miller School.

SIRS is closely related to sepsis, a system-wide infection. Sepsis, known for alterations in body temperature and white blood cell count and a racing heartbeat, is triggered by an infection. SIRS is similar but without any sign of infection, so its cause was never well understood. This study clearly identifies activities in the brain that are relevant to SIRS.

“A lot of diseases of the brain have inflammation as a common mediator, including stroke, Alzheimer’s disease, and SIRS,” says Julio Licinio, M.D., professor and chairman of the Department of Psychiatry and Behavioral Sciences. “So what we show in this paper is that an enzyme, caspase 1, plays a very important role in this inflammatory response.”

“We describe the specific pathways that play a role in inflammation, and they may also play a role in some neuropsychiatric disorders,” says Claudio Mastronardi, Ph.D., a specialist in pharmacogenomics at the Miller School and the lead author on the article.