Editors' ChoiceImmunology

Calming the Gut

Sci. Signal.  11 Oct 2011:
Vol. 4, Issue 194, pp. ec286
DOI: 10.1126/scisignal.4194ec286

Many members of the interluekin-1 (IL-1) family of cytokines, including IL-1β and IL-18, play key roles in stimulating inflammation (see commentary by Kim and Kronenberg). Although proinflammatory responses are beneficial in the short term, long-term inflammation is responsible for such conditions as inflammatory bowel disease (IBD). Therapies that inhibit the effects of proinflammatory cytokines, such as the use of blocking antibodies, provide relief for many, but not all, patients with IBD; thus, further therapies are required. Despite its structural similarity to IL-18, the IL-1 family member IL-37 does not stimulate inflammation; indeed, IL-37 has anti-inflammatory effects in vitro. McNamee et al. studied a role for IL-37 in inflammation in vivo by overexpressing human IL-17 in transgenic mice (hIL-37tg mice) and treating them with dextran sulfate sodium (DSS) to induce colitis, a mouse model of IBD. Breakdown of the epithelial barrier of the colon by DSS was required to induce the expression of the transgene and the production of IL-37 protein. hIL-37tg mice treated with DSS exhibited less severe clinical signs of colitis than did wild-type mice treated with DSS, and this correlated with reduced production of proinflammatory cytokines from colonic explants of hIL-37tg mice. Experiments in which irradiated wild-type mice received bone marrow from either wild-type or hIL-37tg mice showed that IL-37 derived from hematopoietic cells was required to protect mice from DSS-induced colitis. Inducible production of IL-37 also resulted in increased amounts of the anti-inflammatory cytokine IL-10; however, a blocking antibody against the IL-10 receptor did not prevent the protection of hIL-37tg mice from DSS-induced disease. Together, these data suggest that production of IL-37 is part of a feedback mechanism to prevent chronic inflammation in the intestine and provide a potential therapeutic target in the treatment of IBD.

E. N. McNamee, J. C. Masterson, P. Jedlicka, M. McManus, A. Grenz, C. B. Collins, M. F. Nold, C. Nold-Petry, P. Bufler, C. A. Dinarello, J. Rivera-Nieves, Interleukin 37 expression protects mice from colitis. Proc. Natl. Acad. Sci. U.S.A. 108, 16711–16716 (2011). [Abstract] [Full Text]

G. Kim, M. Kronenberg, Cooling the fires of inflammation. Proc. Natl. Acad. Sci. U.S.A. 108, 16493–16494 (2011). [Full Text]