Affiliation:
1. Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
2. Center of Translational Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
Abstract
ObjectiveA fusion protein of interleukin-4 and interleukin-10 (IL4-10 FP) was developed as a disease-modifying osteoarthritis drug (DMOAD), and chondroprotection, anti-inflammation, and analgesia have been suggested. To better understand the mechanisms behind its potential as DMOAD, this systematic narrative review aims to assess the potential of IL-4, IL-10 and the combination of IL-4 and IL-10 for the treatment of osteoarthritis. It describes the chondroprotective, anti-inflammatory, and analgesic effects of IL-4, IL-10, and IL4-10 FP.DesignPubMed and Embase were searched for publications that were published from 1990 until May 21, 2021 (moment of search). Key search terms were: Osteoarthritis, Interleukin-4, and Interleukin-10. This yielded 2,479 hits, of which 43 were included in this review.ResultsIL-4 and IL-10 showed mainly protective effects on osteoarthritic cartilage in vitro and in vivo, as did IL4-10 FP. Both cytokines showed anti-inflammatory effects, but also proinflammatory effects. Only in vitro IL4-10 FP showed purely anti-inflammatory effects, indicating that proinflammatory effects of one cytokine can be counteracted by the other when given as a combination. Only a few studies investigated the analgesic effects of IL-4, IL-10 or IL4-10 FP. In vitro, IL-4 and IL4-10 FP were able to decrease pain mediators. In vivo, IL-4, IL-10, and IL4-10 FP were able to reduce pain.ConclusionsIn conclusion, this review describes overlapping, but also different modes of action for the DMOAD effects of IL-4 and IL-10, giving an explanation for the synergistic effects found when applied as combination, as is the case for IL4-10 FP.
Subject
Physical Therapy, Sports Therapy and Rehabilitation,Biomedical Engineering,Immunology and Allergy
Reference69 articles.
1. Committee for Medicinal Products for Human Use, European Medicines Agency. Guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis. London, UK: European Medicines Agency; 2010.
2. US Food & Drug Administration. Osteoarthritis: structural endpoints for the development of drugs, devices, and biological products for treatment. Guidance for industry. Rockville, MD: US Department of Health & Human Services; 2018.
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