Interleukin‐33 exacerbates acute colitis via interleukin‐4 in mice

Summary Interleukin‐33 ( IL ‐33) and its receptor ST 2 are over‐expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL 33 and ST 2 are the primary early genes induced in the inflamed colon of BALB /c mice following dextran sulphate sodium ( DSS )‐induced experimental ulcerative colitis. Accordingly diarrhoea and DSS ‐induced colon inflammation were impaired in ST 2 −/− BALB /c mice and exacerbated in wild‐type mice by treatment with exogenous recombinant IL ‐33, associated respectively with reduced and enhanced expression of chemokines ( CXCL 9 and CXCL 10), and inflammatory ( IL ‐4, IL ‐13, IL ‐1, IL ‐6, IL ‐17) and angiogenic (vascular endothelial growth factor) cytokines in vivo . The exacerbation effect of treatment with recombinant IL ‐33 on DSS ‐induced acute colitis was abolished in IL ‐4 −/− BALB /c mice. Hence, IL ‐33 signalling via ST 2, by inducing an IL ‐4‐dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis.