Interleukin-37 (IL-37) is an IL-1 family member found in humans, but a mouse homologue has yet to be identified. Unlike other IL-1 family members, IL-37 has emerged as an anti-inflammatory cytokine. To explore the functions of IL-37 in the intestine, the authors induced dextran sulphate sodium (DSS) colitis in a transgenic mouse strain that expresses human IL-37. Compared with controls, IL-37-transgenic mice developed less severe disease, and this was associated with reduced leukocyte infiltration, decreased levels of IL-1β and tumour necrosis factor, and increased levels of IL-10. Interestingly, despite being under the control of a constitutively active promoter, IL-37 expression was only increased in the transgenic mice following DSS-induced tissue damage. Bone marrow chimaera studies showed that the production of IL-37 by bone marrow-derived cells was sufficient to protect mice from DSS-induced colitis. The authors suggest that inducing IL-37 expression in humans may represent a novel therapeutic approach for treating inflammatory bowel disease.