Abstract
BackgroundMcH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16–1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice.MethodsMale McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16–1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines.ResultsTissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16–1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16–1 treated groups.ConclusionsAdministration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.
Highlights
McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle
The purpose of the present study is to investigate the effect of MR16–1 for the treatment of ankle joint arthritis with enthesopathy, and the mechanism of entheseal inflammatory change and ossification in the experimental murine model of McH-lpr/lpr-RA1 mice
enzyme-linked immunosorbent assay (ELISA) assay The results of the ELISA assays showed reduced levels of Serum amyloid A (SAA) in the MR16–1 treatment group at 14 weeks of age, with significantly decreased levels at week 17 (p = 0.04)
Summary
McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16–1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice. Autoimmune arthritis diseases with entheseal inflammation show complex pathological features, including synovitis, bone erosion, enthesitis [1]. Rheumatoid arthritis is characterized by synovial proliferation and erosion of joint cartilage due to chronic inflammation [2]. Autoimmune arthritis with entheseal inflammation like as psoriatic arthrits involves a distinct remodeling process leading to entheseal ossification with synovial proliferation and bone erosion [3, 4]. It is necessary to study animal models of synovitis with intercurrent entheseal ossification to elucidate the pathological mechanisms of the disease, and develop new treatment methods
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