Interleukin-38 is elevated in inflammatory bowel diseases and suppresses intestinal inflammation.

There has been no report investigating the role of IL-38 in inflammatory bowel diseases (IBD). Therefore, we investigated the expression of IL-38 in IBD patients and its role in regulating intestinal inflammation. The levels of IL-38 were significantly elevated in the intestine of IBD patients and DSS-induced colitis mice. Immunofluorescence analysis revealed that B cell, not macrophage or T cell, was the source of IL-38 in the intestine. We found that rIL-38 treatment significantly attenuated DSS-induced colitis, including alleviation of weight loss, disease activity index, macroscopic changes and histological damage of colon, along with lower levels of IL-1β and TNF-α. In vitro, rIL-38 significantly decreased the expression of proinflammatory cytokines in LPS-stimulated RAW 264.7 cells and BMDM. This is the first study suggesting that IL-38 may have a protective effect in IBD, which inhibits the production of proinflammatory cytokines from macrophages. IL-38 may represent a promising therapeutic strategy in IBD.