Anti-interferon-inducible chemokine, CXCL10, reduces colitis by impairing T helper-1 induction and recruitment in mice

Background: Colitis in interleukin (IL)-10(-/-) mice is a CD4(+) T helper 1 (T(H)1)-mediated disease characterized by intermittent, transmural inflammation reminiscent of human Crohn's disease. In this study, we investigated the hypothesis that production of the CXC chemokine CXCL 10 (interferon [IFN]gamma-inducible protein 10) enhances induction of inflammatory responses in draining lymph nodes (LNs) and promotes colonic T(H)1 cell recruitment. Methods: Colitis was induced in B6 IL-10(-/-) mice. Mice were given anti-CXCL10 mAb in 2-week intervals before and after peak colitis. Colitis severity was graded and cytokine/chemokine levels were analyzed by real-time polymerase chain reaction. Cell yields were quantitated and effector cell recruitment was assessed by recovery of transferred D011.10 T(H)1 cells shortly (72 h) after transfer. Results: Treatment with anti-CXCL10 during colitis development decreased clinical and histologic disease severity as well as cytokine/chemokine mRNA and accumulation of mononuclear cells in LNs and colon. Treatment of mice with severe colitis reduced colitis scores and cell yields to lesser degrees. Anti-CXCLIO specifically decreased recruitment of transferred T(H)1 cells into mesenteric LNs (MLNs) and colon of IL-10(-/-) mice by 75% (P < 0.05). Conclusion: These results suggest that CXCL 10 plays a dual role in colitis development by enhancing T(H)1 cell generation in inductive sites and promoting effector cell recruitment to inflamed tissue. Blockade of CXCL 10 may be a useful adjunct to remission-inducing therapies in inflammatory bowel disease (IBD) by impairing disease recurrence through selective inhibition of effector cell generation and trafficking in vivo.