title: Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma.
abstract: Activation of fibroblasts by interleukin-6 (IL-6) is implicated in the pathogenesis of scleroderma, suggesting that the inhibition of fibroblast activation may be a promising scleroderma treatment. In this study, we used an IL-6 blocking antibody (Ab) and Il-6 knockout (Il-6KO) mice to examine the role of IL-6 in the bleomycin (BLM)-induced mouse model of scleroderma. BLM was administered to C57BL/6 and Il-6KO mice to induce dermal sclerosis. BLM-treated and control phosphate-buffered saline-treated mice were treated with anti-mouse IL-6 receptor monoclonal Ab (MR16-1). Disease severity was evaluated by measuring dermal thickness and skin hardness, by counting the numbers of α-smooth muscle actin-positive cells and mast cells, and by examining the cutaneous draining lymph nodes. C57BL/6 mice with BLM induced scleroderma had elevated serum IL-6 levels and more severe dermal sclerosis than Il-6KO mice. Weekly administration of MR16-1, but not control Ab, prevented and improved dermal sclerosis, and also attenuated swelling of the draining lymph nodes. MR16-1 suppressed α-smooth muscle actin induction in IL-6-stimulated Il-6KO fibroblasts. Our results indicate that IL-6 contributes to BLM induced dermal sclerosis and that IL-6 receptor-specific monoclonal Ab may improve the symptoms of scleroderma by suppressing fibroblast activation.
authors: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors: Shun
authors: S
authors: Kitaba
authors: Hiroyuki
authors: H
authors: Murota
authors: Mika
authors: M
authors: Terao
authors: Hiroaki
authors: H
authors: Azukizawa
authors: Fumitaka
authors: F
authors: Terabe
authors: Yoshihito
authors: Y
authors: Shima
authors: Minoru
authors: M
authors: Fujimoto
authors: Toshio
authors: T
authors: Tanaka
authors: Tetsuji
authors: T
authors: Naka
authors: Tadamitsu
authors: T
authors: Kishimoto
authors: Ichiro
authors: I
authors: Katayama
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001761:Bleomycin / Q000633:toxicity; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D012594:Scleroderma, Localized / Q000139:chemically induced / Q000517:prevention & control*; D012598:Sclerosis / Q000139:chemically induced; D012867:Skin / Q000473:pathology
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D011135:Polysaccharides, Bacterial; D019947:Receptors, Interleukin-6; D001761:Bleomycin