IL-6 is required for the development of Th1 cell-mediated murine colitis.
Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn's disease. Among those cytokines, strong expression of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 in the pathogenesis of Crohn's disease, we introduced anti-IL-6R mAb to a murine model of colitis. Colitis was induced in C.B-17-scid mice transferred with CD45RBhigh CD4+ T cells from BALB/c mice. Anti-IL-6R mAb or rat IgG was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expression were analyzed by immunohistochemistry. Colonic cytokine expression was determined by RT-PCR. Mice treated with mAb showed normal growth, whereas controls lost weight. The average colitis score was 0.64 for mAb-treated mice and 1.80 for controls. T cell expansion in treated mice was less remarkable than in the controls. Colonic ICAM-1 and VCAM-1 expression were markedly suppressed by mAb. IFN-gamma, TNF-alpha, and IL-1beta mRNA were reduced by the treatment. The results presented here show a crucial role for IL-6 in the pathogenesis of murine colitis and suggest a therapeutic potential of anti-IL-6R mAb for treatment of human Crohn's disease.
Yamamoto
M
M
Department of Molecular Medicine, Osaka University Medical School, Suita, Japan.
Yoshizaki
K
K
Kishimoto
T
T
Ito
H
H
D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D019947:Receptors, Interleukin-6 / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D019282:Wasting Syndrome / Q000276:immunology / Q000517:prevention & control; D000093242:Interleukin-6 Inhibitors
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D000093242:Interleukin-6 Inhibitors