ANTIINFLAMMATORY PROPERTIES OF INTERLEUKIN-10 ADMINISTRATION IN HAPTEN-INDUCED COLITIS

Therapeutic efficacy of interleukin-10 administration in colonic infla mmation was assessed in rats. Following intracolonic instillation of 2 ,4,6-trinitrobenzene sulfonic acid (TNBS), subcutaneous administration of 1-1000 mu g/kg per day interleukin-10, or a placebo (0.9% NaCl) wa s commenced and continued for 5 days. Interleukin-10 administered at 1 , 10 and 100 mu g/kg per day significantly reduced myeloperoxidase act ivity by 34, 57, and 28%, respectively, compared to the placebo-treate d group, which was paralleled by an attenuation of colonic tumor necro sis factor alpha (TNF-alpha) content. In contrast, the severity of muc osal necrosis was not affected by interleukin-10 administration at the dose range used. In addition, the IO-fold elevation in nitric oxide r elease, 5-fold rise in colonic nitrite production and enhanced express ion of inducible nitric oxide synthase, associated with TNBS colitis, was not suppressed by interleukin-10. Interleukin-10 gene expression w as elevated during the first 14 days of TNBS colitis. We conclude that 5 days administration of interleukin-10 in TNBS colitis displays mild anti-inflammatory properties which were not mediated via a nitric oxi de-dependent pathway, but may involve TNF-alpha.