title: IL-4 exacerbates disease in a Th1 cell transfer model of colitis.
abstract: IL-4 is associated with Th2-type immune responses and can either inhibit or, in some cases, promote Th1-type responses. We tested the effect of IL-4 treatment on the development of inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis, which has been characterized as a Th1-dependent disease. IL-4 treatment significantly accelerated the development of colitis in immunodeficient recipients (recombinase-activating gene-2 (Rag2)(-/-)) of CD4(+)CD45RB(high) T cells. Quantitative analysis of mRNA expression in the colons of IL-4-treated mice showed an up-regulation of both Th1- and Th2-associated molecules, including IFN-gamma, IP-10, MIG, CXCR3, chemokine receptor-8, and IL-4. However, cotreatment with either IL-10 or anti-IL-12 mAb effectively blocked the development of colitis in the presence of exogenous IL-4. These data indicate that IL-4 treatment exacerbates a Th1-mediated disease rather than induces Th2-mediated inflammation. As other cell types besides T cells express the receptor for IL-4, the proinflammatory effects of IL-4 on host cells in Rag2(-/-) recipients were assessed. IL-4 treatment was able to moderately exacerbate colitis in Rag2(-/-) mice that were reconstituted with IL-4Ralpha-deficient (IL-4Ralpha(-/-)) CD4(+)CD45RB(high) T cells, suggesting that the IL-4 has proinflammatory effects on both non-T and T cells in this model. IL-4 did not cause colitis in Rag2(-/-) mice in the absence of T cells, but did induce an increase in MHC class II expression in the lamina propria of the colon, which was blocked by cotreatment with IL-10. Together these results indicate that IL-4 can indirectly promote Th1-type inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis.
authors.affiliation: Department of Molecular Biology, DNAX Research Institute for Molecular and Cellular Biology, Palo Alto, CA 94304, USA. fort@dnax.org
authors.forename: M
authors.initials: M
authors.lastname: Fort
authors.forename: R
authors.initials: R
authors.lastname: Lesley
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.forename: S
authors.initials: S
authors.lastname: Menon
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
authors.forename: M
authors.initials: M
authors.lastname: Leach
authors.forename: D
authors.initials: D
authors.lastname: Rennick
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D006965:Hyperplasia; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000172:deficiency / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D015847:Interleukin-4; D017493:Leukocyte Common Antigens