Interleukin-1β Mediates the Extra-Intestinal Thrombosis Associated with Experimental Colitis

Inflammatory bowel diseases (IBDs) are associated with an increased risk for thromboembolism, which is often manifested as deep vein thrombosis or pulmonary embolism at extra intestinal sites Although some of the cytokines that contribute to IBD pathogenesis are also known to alter the coagulation path way it remains unclear whether these mediators also contribute to the extra intestinal thrombosis often associated with IBD The objective of this study is to evaluate the role of interleukin (IL) 1 beta in enhanced extra intestinal thrombosis observed m mice with dextran sodium sulfate (DSS) induced colitis IL 1 beta concentrations were measured m plasma colon and skeletal muscle of wild type (WT) control and colitic mice Microvascular thrombosis was induced in cremaster muscle microvessels by using a light/dye in jury model The effects of exogenous IL-1 beta on thrombus formation were determined in control WT mice DSS induced thrombogenesis was evaluated in WT mice treated with an IL 1 beta antibody and in IL 1 receptor deficient (IL-1r(-/-)) mice DSS induced colonic inflammation in WT mice was associated with enhanced thrombus formation in arterioles IL-1 beta concentrations were elevated in inflamed colon and skeletal muscle Exogenous IL 1 beta enhanced thrombosis in control mice m a dose dependent manner DSS colitic mice treated with the IL 1 beta antibody as well as IL 1r(-/-) mice exhibited significantly blunted thrombogenic responses These findings implicate IL 1 beta as a mediator of enhanced microvascular thromboses that occur in extra intestinal tissues during colonic inflammation (Am J Pathol 2010 177 2774-2781 DOI 10 2353/ajpath 2010 100205)