Relationship of Interleukin-1 Receptor Antagonist to Mucosal Inflammation in Inflammatory Bowel Disease

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Abstract
Summary: Previous work has suggested that the interleu-kin-1 (IL-1) receptor antagonist, IL-Ira, may regulate mucosal inflammation in inflammatory bowel disease. The present study assessed the relationship of mucosal IL-Ira levels to histologic severity of inflammation and the related proinflammatory cytokines IL-1β and IL-6 in children with inflammatory bowel disease. Colonic biopsy specimens from 29 patients with ulcerative colitis, 27 with Crohn's disease, and 24 noninflammatory control subjects were assayed for IL-Ira, IL-1β, and IL-6 by enzyme-linked immunosorbent assay. Histologic activity was graded as none, mild, moderate, or severe. Mucosal IL-1β levels, but not IL-lra levels, were significantly elevated in moderate/severely inflamed biopsies from patients with either ulcerative colitis (p < 0.01) or Crohn's disease (p < 0.001) compared with those with none/mild inflammation. The mucosal molar ratio of IL-lra/IL-1β was significantly lower for moderate/severe inflammation compared with none/mild inflammation for patients with ulcerative colitis (p < 0.05) and Crohn's disease (p < 0.01). The mucosal IL-lra/IL-1β ratio was similar in controls to none/mild inflamed biopsies from subjects with either ulcerative colitis or Crohn's disease. Our observations suggest that increasing mucosal inflammation in inflammatory bowel disease in children is associated with a decrease in the “normal” effective IL-lra/IL-1β ratio in which IL-lra predominates. The importance of this abnormality to the pathogencsis of inflammatory bowel disease awaits further study.

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