ABSTRACT
Purpose of the study
Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA.
Materials and Methods
The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis.
Results
Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue.
Conclusions
The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.
Acknowledgments
Micro-CT services were provided by the InfrafrontierGR Research infrastructure located at Biomedical Sciences Research Centre Alexander Fleming, which is co-funded by Greece and the European Union (European Region Development Fund) under the Operational Program “Competitiveness, Entrepreneurship and Innovation” of the NSRF 2014–2020. We thank Athanasia Pappa, president of the Hellenic League Against Rheumatism, for her contribution during various stages of the research project. We, also, thank Professor Mary Barbe from the Department of Anatomy and Cell Biology, Temple University, for her guidance on how to handle tendon tissue samples and perform the ELISA experiments.
Data availability statement
The data underlying this article will be shared on reasonable request to the corresponding author.
Disclosure statement
No potential conflict of interest was reported by the author(s).