Tess and his colleagues have now tracked this connection: After a burst of stress, the brain sends signals to the adrenal glands, which release certain chemicals, called glucocorticoids, to the rest of the body. Initially, the researchers hypothesized that glucocorticoids act directly on immune cells in the gut, which then release molecules that cause inflammation. “It turns out, though, that there is a kind of middle class,” Tess says. Working with mice, the group found that glucocorticoids act instead on neurons in the gut and glial cells, which connect neurons in the gut together.
Glucocorticoids: A double-edged sword when it comes to inflammation
After being activated by glucocorticoids, some glial cells release molecules that activate immune cells. These immune cells then release molecules that are normally used to fight off pathogens, but in this case lead to painful intestinal inflammation. At the same time, glucocorticoids inhibit the development of immature neurons in the intestine. As a result, these neurons produce only small amounts of the signaling molecules that cause the intestinal muscles to contract. This causes food to move more slowly through the digestive tract, adding to the symptoms of IBD.
Researchers were surprised to discover that glucocorticoids apparently can cause intestinal inflammation. Because glucocorticoids are sometimes used to treat inflammatory bowel disease. This apparent paradox may be explained by the short period of time in which such therapies are typically used: Although rapid bursts of glucocorticoids appear to be anti-inflammatory, the system turns on completely when stress becomes chronic. Theis says glucocorticoids take on an inflammatory role. Gastroenterologist and immunologist John Chang of the University of California, San Diego, considered this a plausible explanation.