COLONIC EXPLANT PRODUCTION OF IL-1 AND ITS RECEPTOR ANTAGONIST IS IMBALANCED IN INFLAMMATORY BOWEL-DISEASE (IBD)

IBD is associated with an increased activation of intestinal immune ce lls, which causes overproduction of proinflammatory cytokines such as IL-1 beta. IL-1 beta is implicated in mediating the sustained inflamma tory response. IL-1 receptor antagonist (IL-1Ra), the naturally occurr ing inhibitor of IL-1, has been shown to have beneficial effects in ex perimental models of colitis. In this study we investigated the hypoth esis that an imbalance between IL-1 and IL-1Ra exists in IBD by measur ing their secretion by explant cultures of colonic biopsies. Freshly h omogenized biopsies from involved tissue in IBD patients exhibited sig nificantly lower IL-1Ra/IL-1 beta ratios than control and uninvolved I BD mucosal tissue. Using explant cultures, in vitro production of IL-1 beta and IL-1Ra increased progressively during the 4-18-h culture per iods. IL-IP secretion was higher in supernatants from involved Crohn's disease (CD) and ulcerative colitis tissue compared with control tiss ue, and IL-IP levels increased with severity of inflammation. IL-1Ra s ecretion was not elevated in involved IBD samples, but significantly h igher levels were released when moderate to severely involved tissue s amples were compared with noninflammatory controls. Similar to freshly homogenized tissue, explant studies showed that the IL-1Ra/ IL-IP rat ios were significantly decreased in involved IBD tissue, but not in un involved CD or inflammatory control specimens. These data support the hypothesis of an imbalance between IL-1 beta and IL-1Ra in IBD.