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Am J Pathol. 2012 Jan;180(1):165-76. doi: 10.1016/j.ajpath.2011.09.013. Epub 2011 Nov 7.

Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma.

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  • 1Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.

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.

Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID:
22062222
[PubMed - indexed for MEDLINE]
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