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

Academic Article


  • BACKGROUND: Colitis in interleukin (IL)-10 mice is a CD4 T helper 1 (TH1)-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 CXCL10 (interferon [IFN]gamma-inducible protein 10) enhances induction of inflammatory responses in draining lymph nodes (LNs) and promotes colonic TH1 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 TH1 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-CXCL10 specifically decreased recruitment of transferred TH1 cells into mesenteric LNs (MLNs) and colon of IL-10 mice by 75% (P<0.05). CONCLUSION: These results suggest that CXCL10 plays a dual role in colitis development by enhancing TH1 cell generation in inductive sites and promoting effector cell recruitment to inflamed tissue. Blockade of CXCL10 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.
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    Published In


  • Animals, Antibodies, Monoclonal, Chemokine CXCL10, Chemokines, CXC, Colitis, Inflammation, Male, Mice, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Th1 Cells
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    Author List

  • Hyun JG; Lee G; Brown JB; Grimm GR; Tang Y; Mittal N; Dirisina R; Zhang Z; Fryer JP; Weinstock JV
  • Start Page

  • 799
  • End Page

  • 805
  • Volume

  • 11
  • Issue

  • 9