IL4-10 fusion protein has chondroprotective, anti-inflammatory and potentially analgesic effects in the treatment of osteoarthritis
Steen-Louws, C.; Popov-Celeketic, J.; Mastbergen, S. C.; Coeleveld, K.; Hack, C. E.; Eijkelkamp, N.; Tryfonidou, M.; Spruijt, S.; van Roon, J. A.G.; Lafeber, F. P.J.G.
(2018) Osteoarthritis and Cartilage, volume 26, issue 8, pp. 1127 - 1135
(Article)
Abstract
Objective: Effective disease-modifying drugs for osteoarthritis (DMOAD) should preferably have chondroprotective, anti-inflammatory, and analgesic activity combined in a single molecule. We developed a fusion protein of IL4 and IL10 (IL4-10 FP), in which the biological activity of both cytokines is preserved. The present study evaluates the chondroprotective, anti-inflammatory, and analgesic
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activity of IL4-10 FP in in vitro and in vivo models of osteoarthritis. Methods: Human osteoarthritic cartilage tissue and synovial tissue were cultured with IL4-10 FP. Cartilage proteoglycan turnover and release of pro-inflammatory, catabolic, and pain mediators by cartilage and synovial tissue were measured. The analgesic effect of intra-articularly injected IL4-10 FP was evaluated in a canine model of osteoarthritis by force-plate analysis. Results: IL4-10 FP increased synthesis (P = 0.018) and decreased release (P = 0.018) of proteoglycans by osteoarthritic cartilage. Release of pro-inflammatory IL6 and IL8 by cartilage and synovial tissue was reduced in the presence of IL4-10 FP (all P < 0.05). The release of MMP3 by osteoarthritic cartilage and synovial tissue was decreased (P = 0.018 and 0.028) whereas TIMP1 production was not significantly changed. Furthermore, IL4-10 FP protected cartilage against destructive properties of synovial tissue mediators shown by the increased cartilage proteoglycan synthesis (P = 0.0235) and reduced proteoglycan release (P = 0.0163). Finally, intra-articular injection of IL4-10 FP improved the deficient joint loading in dogs with experimentally induced osteoarthritis. Conclusion: The results of current preliminary study suggest that IL4-10 FP has DMOAD potentials since it shows chondroprotective and anti-inflammatory effects in vitro, as well as potentially analgesic effect in a canine in vivo model of osteoarthritis.
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Keywords: Cartilage, Cytokines, DMOAD, Osteoarthritis, Pain, Osteoarthritis/drug therapy, Proteoglycans/metabolism, Humans, Cells, Cultured, Cartilage, Articular/cytology, Male, Interleukin-10/therapeutic use, Recombinant Proteins, Anti-Inflammatory Agents/therapeutic use, Animals, Interleukin-4/therapeutic use, Dogs, Female, Synovial Membrane/cytology, Analgesics/therapeutic use, Disease Models, Animal, Biomedical Engineering, Rheumatology, Orthopedics and Sports Medicine, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 1063-4584
Publisher: W.B. Saunders Ltd
Note: Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
(Peer reviewed)