Influence of interleukin-10 on the interleukin-1 receptor antagonist/interleukin-1 beta ratio in the colonic mucosa of ulcerative colitis

A decrease in the ratio of IL-1ra/IL-1 beta produced regionally by the colo nic mucosa of patients with ulcerative colitis (UC) is believed to play a r ole in the pathogenesis of UC. To investigate factors influencing intramuco sal IL-1ra/IL-1 beta ratios, we evaluated polymorphism of the IL-1ra gene a nd the production of mucosal cytokines in Japanese patients with UC. Coloni c biopsy specimens of mucosal tissue were placed in organ cultures for 24 h . Then, the supernatant concentrations of IL-1 beta, IL-1ra, IL-8, IL-4, IL -10, and TGF-B were assayed by ELISA. Genomic DNA was extracted from patien t peripheral blood samples, then IL-1ra gene polymorphism was determined us ing PCR amplification. The mucose from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1 beta ratio. In the resolving sta ge, IL-1ra/IL-1 beta ratios increased with increasing IL-10 and TGF-beta co ncentrations. The addition of human recombinant IL-10 to the culture supern atants produced concentration-dependent inhibition of IL-1 beta. In Japanes e patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1 beta ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory change s. Copyright (C) 2001 S. Karger AG, Basel.