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: Shun Kitaba, Hiroyuki Murota, Mika Terao, Hiroaki Azukizawa, Fumitaka Terabe, Yoshihito Shima, Minoru Fujimoto, Toshio Tanaka, Tetsuji Naka, Tadamitsu Kishimoto, Ichiro Katayama
• Journal: The American journal of pathology (Am J Pathol) Vol. 180 Issue 1 Pg. 165-76 (Jan 2012) ISSN: 1525-2191 [Electronic] United States
• PMID: 22062222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Acta2 protein, mouse
• Actins
• Antibiotics, Antineoplastic
• Antibodies, Monoclonal
• Polysaccharides, Bacterial
• Receptors, Interleukin-6
• Bleomycin

Topics

• Actins (metabolism)
• Animals
• Antibiotics, Antineoplastic (toxicity)
• Antibodies, Monoclonal (pharmacology)
• Bleomycin (toxicity)
• Cells, Cultured
• Female
• Fibroblasts (metabolism)
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Polysaccharides, Bacterial (pharmacology)
• Receptors, Interleukin-6 (antagonists & inhibitors)
• Scleroderma, Localized (chemically induced, prevention & control)
• Sclerosis (chemically induced)
• Skin (pathology)