Colonic explant production of IL-1 and its receptor antagonist is imbalanced in inflammatory bowel disease (IBD)

Abstract

SUMMARY IBD is associated with an increased activation of intestinal immune cells, which causes overproduction of proinflammatory cytokines such as IL-1β. IL-1β is implicated in mediating the sustained inflammatory response. IL-1 receptor antagonist (IL-1Ra), the naturally occurring inhibitor of IL-1, has been shown to have beneficial effects in experimental models of colitis. In this study we investigated the hypothesis that an imbalance between IL-1 and IL-1Ra exists in IBD by measuring their secretion by explant cultures of colonic biopsies. Freshly homogenized biopsies from involved tissue in IBD patients exhibited significantly lower IL-1Ra/IL-1β ratios than control and uninvolved IBD mucosal tissue. Using explant cultures, in vitro production of IL-1β and IL-1Ra increased progressively during the 4–18-h culture periods. IL-1β secretion was higher in supernatants from involved Crohn's disease (CD) and ulcerative colitis tissue compared with control tissue, and IL-1β levels increased with severity of inflammation. IL-1Ra secretion was not elevated in involved IBD samples, but significantly higher levels were released when moderate to severely involved tissue samples were compared with non-inflammatory controls. Similar to freshly homogenized tissue, explant studies showed that the IL-1Ra/IL-1β ratios were significantly decreased in involved IBD tissue, but not in uninvolved CD or inflammatory control specimens. These data support the hypothesis of an imbalance between IL-1β and IL-1Ra in IBD.