Stress has been associated with a variety of health issues, ranging from insomnia and high blood pressure to obesity and even heart disease. However, scientists have also acknowledged that some stress – like when someone is chasing a work deadline – can be helpful. Now, a team of researchers led by Case Western Reserve University has found that the immune system may benefit from a measure of stress.
“This is one of the few studies showing that chronic stress could have beneficial effect instead of negative effect,” said study senior author Fabio Cominelli, a professor of Medicine and Pathology at Case Western.
In recent years, psychological stress has been found to exacerbate symptoms of inflammatory bowel disease (IBD). Similarly, the immune cells which form in response to chronic inflammation or injury – called intestinal tertiary lymphoid organs (TLOs) – are generally associated with increased inflammation. However, TLO formation in response to stress has not been yet studied.
Now, the Case Western experts discovered that, after 56 days of stress, mouse models with Crohn’s disease-like ileitis exhibited increased TLO formation in the colon as an immune response, while stress did not significantly increase small or large intestine inflammation. The scientists found that the microbiome of the stressed mice was compositionally similar to those in a control group.
However, after a fecal microbiome transplantation, mice receiving the microbiome of stressed mice had the same behavioral phenotype as their donors and transplantation did not increase TLO formation. Instead, stress seemed to increase production of the cytokines IL-23 and IL-22, which are an essential part of the TLO formation pathway, with IL-22 playing a protective role in wound-healing and can have both anti- and pro-inflammatory responses.
Stressed mice with deficiencies in the receptor for IL-23 had increased IL-23, but not IL-22, and were not able to increase TLO formation. However, when IL-22 was administered, this effect was reversed. Considering the link between TLOs and various diseases, the researchers believed that stressed mice would be more susceptible to a “second hit” in the colon. Surprisingly though, stressed mice seemed to actually exhibit less severe inflammation after this “second hit.”
“Our findings demonstrate that psychological stress induces formation of TLOs by increasing the production of IL-23. Furthermore, the stressed mice were protected after a ‘second hit,’ suggesting TLOs may function to improve the mucosal barrier,” Professor Cominelli explained.
“What we discovered it that chronic daily stress for six weeks was beneficial against a second injury. The mouse models that were stressed were actually protected. We showed they had stimulation of the immune system, which protects against intestinal inflammation. What needs to be studied is whether this may translate to other diseases and injuries.”
“So do I want to be stressed? It all depends on the definition of stress. ‘Stimulated’ is a better term. The message is that a little bit of stress is good in your life, but you want to be stressed in the right way,” he concluded.
The study is published in the journal Proceedings of the National Academy of Sciences.
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