Blockade of interleukin‐6 receptor enhances the anti‐arthritic effect of glucocorticoids without decreasing bone mineral density in mice with collagen‐induced arthritis. (31st August 2015)

• Record Type: Journal Article
• Authors: Suzuki, M.; Yoshida, H.; Hashizume, M.; Tanaka, K.; Matsumoto, Y.
• Is Part Of: Clinical and experimental immunology. Volume 182:Number 2(2015:Nov.)
• Page Start: 154
• Page End: 161
• Publication Date: 2015-08-31
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12685
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>In a mouse arthritis model, we investigated whether interleukin‐6 receptor (IL‐6R) blockade would enhance the anti‐arthritic effect of glucocorticoids (GCs). DBA/1J mice were immunized with type II collagen (CII), and were treated with prednisolone (PSL) and/or anti‐mouse IL‐6R antibody (MR16‐1). Also, the effects of IL‐6 on gene expression and the nuclear translocation of glucocorticoid receptors (GRs) were examined in cultured cells treated with dexamethasone (DEX). PSL reduced the arthritis score dose‐dependently in the collagen‐induced arthritis (CIA) mouse model. The arthritis score in the PSL (3 mg/kg) + MR16‐1 group was lower than in the PSL (3 mg/kg) group, and at the same level as in the PSL (6 mg/kg) group. Lumbar vertebra bone mineral density (BMD) was decreased significantly in CIA mice and was higher in the PSL (3 mg/kg) + MR16‐1 group than in the PSL (6 mg/kg) group. In the <italic>in‐vitro</italic> synovial cells, IL‐6 pretreatment attenuated the inhibitory effect of DEX on cyclooxygenase (COX)‐2 expression and inhibited the nuclear translocation of GR induced by DEX. In contrast, in MC3T3‐E1 osteoblastic cells, IL‐6 pretreatment exacerbated the decrease in expression of osteocalcin and the increase in expression of receptor activator of nuclear factor kappa‐B ligand (RANKL) by DEX. We demonstrated that IL‐6 signalling blockade by an anti‐IL‐6R antibody can augment the anti‐arthritic effect of GCs and inhibit the bone loss they cause.</p> </abstract>