Yale University study solves mystery about how stress triggers inflammation

A new study led by scientists at Yale University has solved a long-standing mystery that while many stress hormones actually suppress the immune system, acute stress seems to amplify inflammatory diseases. The study revealed that a particular immune cell is released by fat cells when the body is under systemic stress.

Yale University study solves mystery about how stress triggers inflammation

For decades, the link between stress and inflammatory diseases has been clear, and many chronic diseases are apparently triggered by acute stress. However, on the basis of this clear observation, there has always been an inexplicable paradox that hormones released by the body, such as cortisol and epinephrine, have a significant immunosuppressive effect when faced with stress, but stress still seems to stimulate inflammation.

“Clinically, we’ve all seen super stress events that make inflammatory diseases worse, and that never meant to us. Andrew Wang, the study’s author, explains.

The new study stems from a new laboratory observation. Taking blood samples from mice was an inherent stress process, and the researchers noted that this was associated with an increase in interleukal interleukin-6 (IL-6) levels. The increase in IL-6 levels has previously been associated with autoimmune conditions and acute stress, but how it was released has not been studied.

Yale University study solves mystery about how stress triggers inflammation

New research described by one of the authors as “completely unexpected” shows that IL-6 is secreted by brown fat cells in the face of acute stress. When we are under stress, it is this immune mechanism that amplifies inflammation. When the signaling between the mouse’s brain and brown fat cells was blocked, the animals no longer had an inflammatory response when faced with stress situations.

But one question remains unanswered — what evolutionary function explains why stress triggers such a destructive immune system mechanism? The researchers found that IL-6 played a fundamental role in medialing hypoglycemia. Essentially, this helps prepare the body for an increase in glucose production, which is essential fuel for our “fight or escape” response. From an evolutionary perspective, the study explains, “this adaptation comes at the expense of increasing mortality from subsequent inflammatory challenges.”

As a result, these findings provide a compelling new avenue for research, not only for some autoimmune diseases, but also for many mental health disorders. When IL-6 was blocked in mice, the animal’s signs of restlessness decreased significantly, suggesting that immune mechanisms may play a role in anxiety and depression.

IL-6 inhibitors already exist and have been used to treat autoimmune diseases such as rheumatoid arthritis. Tocilizumab, the FDA-approved first IL-6 inhibitor, is already being tested as an antidepressant treatment.

The new study was published in the journal Cell.