MUCOSAL IMBALANCE OF IL-1 AND IL-1 RECEPTOR ANTAGONIST IN INFLAMMATORY BOWEL-DISEASE - A NOVEL MECHANISM OF CHRONIC INTESTINAL INFLAMMATION

The etiology and pathogenesis of inflammatory bowel disease (IBD) are unknown. Increasing evidence supports the theory that chronic IBD is t he result of dysfunctional immunoregulation manifested by an inappropr iate production of mucosal cytokines. The aim of the present study was to test the hypothesis that a specific mucosal imbalance of IL-1 and IL-1 receptor antagonist (IL-1ra) production plays an important role i n the perpetuation and chronicity of intestinal inflammation. Total IL -1, IL-1ra, and the IL-1ra/IL-1 ratio were measured in freshly isolate d intestinal mucosal cells, as well as in mucosal biopsies obtained fr om control, Crohn's disease, and ulcerative colitis patients. IL-1 alp ha, IL-1 beta, and IL-1ra were measured by specific non-cross-reacting radioimmunoassays and ELISA. A markedly significant decrease in the i ntestinal mucosal IL-1ra/IL-1 ratio was found in both Crohn's disease and ulcerative colitis patients when compared with control subjects (p < 0.01). The IL-1ra/IL-1 ratio correlated closely with the clinical s everity of disease (r = -0.7846, p < 0.001). Furthermore, the observed decrease in the IL-1ra/IL-1 ratio was specific for IBD because a decr eased IL-1ra/IL-1 ratio was not found in patients with self-limiting c olitis. These results support the hypothesis that an imbalance between IL-1 and IL-1ra production is of pathogenic importance in chronic inf lammatory diseases, including IBD.