A new Yale University-led study has solved a long-standing mystery of how acute stress seems to amplify inflammatory disease despite the fact many stress hormones actually suppress the immune system. The research reveals a particular immune cell is released by fat cells when an organism faces systemic stress.
For several decades a link between stress and inflammatory disease has been clear, with many chronic diseases obviously triggered into flare-ups by acute periods of stress. However, underlying this clear observation has been an unexplained paradox; hormones released by the body in the face of stress, such as cortisol and adrenaline, confer distinctly immunosuppressive effects, yet stress somehow still seems to stimulate inflammation.
“In the clinic, we have all seen super-stressful events that make inflammatory disease worse, and that never made sense to us,” explains corresponding author on the study, Andrew Wang.
The new study stemmed from a novel laboratory observation. Taking blood samples from mice is an inherently stressful procedure and the researchers noticed this correlated with an increase in interleukin-6 (IL-6) levels. Increased IL-6 levels have previously been implicated in autoimmune conditions and acute stress, but exactly how it is released has not been studied.
The results of the new research, described as “completely unexpected” by one of the authors, reveal IL-6 is secreted by brown fat cells in the face of acute stress. It’s this immune mechanism that amplifies inflammation when we face a stressful situation. And, when signaling between the brain and brown fat cells was blocked in mice, the animals no longer showed inflammatory responses when presented with stressful situations.
But one question still remained unanswered – what evolutionary function explains why stress triggers such a damaging immune system mechanism?
Here, the researchers discovered IL-6 plays a fundamental role in mediating hypoglycemia. Essentially, this helps prepare the body for increases in glucose production necessary as fuel for our “fight or flight” response. The study explains, from an evolutionary perspective, “this adaptation comes at the cost of enhancing mortality to a subsequent inflammatory challenge.”
Therefore, these findings offer compelling and novel research pathways, not only for a number of autoimmune conditions, but also for many mental health disorders. When IL-6 was blocked in the mice the animals displayed significant reductions in signs of agitation, suggesting the immune mechanism may play a role in anxiety and depression.
IL-6-inhibiting drugs already exist, and have been used to treat autoimmune conditions such as rheumatoid arthritis. Tocilizumab, the first FDA-approved IL-6 inhibitor, is already being trialed as an anti-depressant therapy.
The new research was published in the journal Cell.
Source: Yale University
