Interleukin-6 genetic ablation protects from trinitrobenzene sulfonic acid-induced colitis in mice. Putative effect of antiinflammatory cytokines.

BACKGROUND

Interleukin (IL)-6 is a proinflammatory cytokine implicated in the pathogenesis of inflammatory bowel disease. IL-6 is locally upregulated in inflammatory bowel disease patients and in murine models of experimental colitis. Treatment with anti-IL-6 receptor antibody ameliorates intestinal inflammation.

OBJECTIVE

It was the aim of this study to investigate the role of genetic IL-6 deficiency in trinitrobenzene sulfonic acid (TNBS)-mediated colitis, an experimental model inflammation that shares several features with Crohn's disease in humans.

METHODS

Acute colitis was induced in wild-type and IL-6-deficient (Il-6(-/-)) mice by intracolonic administration of TNBS. Forty-eight hours after treatment, the local and systemic features of inflammation, i.e. food intake, weight loss, histological markers of colitis, cytokine expression by real-time PCR, food intake and body weight changes, were assessed.

RESULTS

In wild-type mice, TNBS administration increased both IL-6 serum levels and local expression of IL-6 by 36 and 9 fold, respectively, compared with control, vehicle-injected mice. Compared with the wild-type mice, the Il-6(-/-) mice had significantly reduced intestinal inflammation as evidenced by epithelial damage, neutrophil infiltration, colon thickness and proinflammatory cytokine expression, following treatment with TNBS. Moreover, baseline levels of the antiinflammatory cytokines IL-10 and tumor growth factor-beta were significantly elevated in Il-6(-/-)compared with the wild-type mice.

CONCLUSIONS

Our results demonstrate that Il-6(-/-)are partially protected from the development of TNBS-induced acute experimental colitis, most likely via their significantly elevated baseline levels of antiinflammatory cytokines.