IL-1β inhibition combined with cholesterol-lowering therapies decreases synovial lining thickness and spontaneous cartilage degeneration in a humanized dyslipidemia mouse model.

Autor: van Gemert Y; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Kruisbergen NNL; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Blom AB; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., van den Bosch MHJ; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., van der Kraan PM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Pieterman EJ; Metabolic Health Research, TNO, Leiden, the Netherlands., Princen HMG; Metabolic Health Research, TNO, Leiden, the Netherlands., van Lent PLEM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: peter.vanlent@radboudumc.nl.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2023 Mar; Vol. 31 (3), pp. 340-350. Date of Electronic Publication: 2022 Nov 25.
DOI: 10.1016/j.joca.2022.09.014
Abstrakt: Introduction: Both systemic inflammation and dyslipidemia contribute to osteoarthritis (OA) development and have been suggested as a possible link between metabolic disease and OA development. Recently, the CANTOS trial showed a reduction in knee and hip replacements after inhibition of IL-1β in patients with a history of cardiovascular disease and high inflammatory risk. In this light, we investigated whether inhibition of IL-1β combined with cholesterol-lowering therapies can reduce OA development in dyslipidemic APOE∗3Leiden mice under pro-inflammatory dietary conditions.
Materials and Methods: Female ApoE3∗Leiden mice were fed a cholesterol-supplemented Western-Type diet (WTD) for 38 weeks. After 14 weeks, cholesterol-lowering and anti-inflammatory treatments were started. Treatments included atorvastatin alone or with an anti-IL1β antibody, and atorvastatin combined with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor alirocumab without or with the anti-IL1β antibody. Knee joints were analyzed for cartilage degradation, synovial inflammation and ectopic bone formation using histology at end point.
Results: Cholesterol-lowering treatment successfully decreased systemic inflammation in dyslipidemic mice, which was not further affected by inhibition of IL-1β. Synovial thickening and cartilage degeneration were significantly decreased in mice that received cholesterol-lowering treatment combined with inhibition of IL-1β (P < 0.01, P < 0.05, respectively) compared to mice fed a WTD alone. Ectopic bone formation was comparable between all groups.
Conclusion: These results indicate that inhibition of IL-1β combined with cholesterol-lowering therapy diminishes synovial thickening and cartilage degeneration in mice and may imply that this combination therapy could be beneficial in patients with metabolic inflammation.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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