title: Anti-interferon-inducible chemokine, CXCL10, reduces colitis by impairing T helper-1 induction and recruitment in mice.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Northwestern University School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Jae Geun
authors.initials: JG
authors.lastname: Hyun
authors.forename: Goo
authors.initials: G
authors.lastname: Lee
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Brown
authors.forename: Gery R
authors.initials: GR
authors.lastname: Grimm
authors.forename: Yueming
authors.initials: Y
authors.lastname: Tang
authors.forename: Navhda
authors.initials: N
authors.lastname: Mittal
authors.forename: Ramanarao
authors.initials: R
authors.lastname: Dirisina
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Fryer
authors.forename: Joel V
authors.initials: JV
authors.lastname: Weinstock
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Terrence A
authors.initials: TA
authors.lastname: Barrett
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000502:physiology*; D003092:Colitis / Q000276:immunology*; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse