FRI0035 Joint Inflammation and Cartilage Destruction in Experimental Osteoarthritis Is Not Mediated by Interleukin-1. (15th July 2016)

• Record Type: Journal Article
• Authors: Van Dalen, S.; Blom, A.; Joosten, L.; Sloetjes, A.; Helsen, M.; van den Berg, W.; van Lent, P.
• Is Part Of: Annals of the rheumatic diseases. Volume 75(2016)Supplement 2
• Page Start: 438
• Page End: 438
• Publication Date: 2016-07-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2016-eular.3500
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Osteoarthritis (OA) is a degenerative disease of the joint characterized by severe cartilage destruction, with a putative role for synovial macrophages. Up to 50% of the patients also show low grade joint inflammation reflected by a thickened synovial lining and elevated release of macrophage-derived mediators like interleukin-1 (IL-1) and S100A8/A9. The deteriorating role of S100A8/A9 in OA has been studied extensively (1), but the contribution of IL-1 to OA pathology is still unclear. IL-1 mediates cartilage destruction by degrading existing proteoglycans through stimulating degradative enzyme production, and by inhibiting new formation of proteoglycans. However, treatment of OA patients with IL-1 inhibitors has so far been disappointing. Objectives: To investigate the role of IL-1α/β in synovitis and cartilage destruction during experimental collagenase-induced OA (CiOA). Methods: Experimental OA was induced by intra-articular injection of collagenase into WT and IL-1αβ –/– mice. At day 7 and 42 after CiOA induction, total knee joints were stained with haematoxylin/eosin (H&E) to score synovial activation (arbitrary score from 0–3). Cartilage destruction was determined in knee sections stained with safranin O/fast green using a modified Pritzker score. Gene expression in inflamed synovium was analyzed using qPCR with primers for several cytokines. Serum protein levels of inflammatory mediators were measured with Luminex. Results: At early stage (day 7) of CiOA, gene expression of IL-1 within inflamed synovium of knee joints was elevated 65 times compared to synovium of naïve control knees. However in later stages (day 21 and 42), IL-1 expression levels were reduced to basal levels. This is in contrast to pro-inflammatory mediators like S100A8 and S100A9 which remained elevated at day 21 and 42 (30–35-fold and 66–69-fold, respectively). Histological examination of knee joints showed a moderate synovitis at day 7 which waned thereafter but was still significant at day 21 and 42. Remarkably, synovial inflammation at day 7 in IL-1αβ –/– mice was not different from WT controls (2.89±0.15 vs. 2.71±0.44), suggesting that IL-1 does not aggravate synovitis. Absence of IL-1α/β had no effect on the synovial gene expression levels of pro-inflammatory factors KC, S100A8 and S100A9. IL-6 mRNA levels, however, were significantly decreased in the synovium of IL-1αβ –/– mice (3-fold reduction). The lack of IL-1α/β also did not affect gene expression of anti-inflammatory cytokines IL-10, TGFβ and iNOS. Moreover, serum protein levels of KC, IL-6, MCP-1, IL-10 and S100A8/A9 at day 7 of CiOA in IL-1αβ –/– mice were not different compared to WT mice. Cartilage destruction in CiOA clearly aggravated over time, but we found no significant differences between IL-1αβ –/– mice and WT controls. No difference in cartilage damage was measured at day 42 of CiOA when compared to WT (medial femur (95.3±42.0 vs. 65.5±54.5), medial tibia (84.5±36.6 vs. 55.1±38.9), lateral femur (69.6±43.9 vs. 60.8±35.8), and lateral tibia (49.8±26.3 vs. 55.4±17.1)). Conclusions: IL-1 does not affect synovial inflammation and cartilage destruction during collagenase-induced osteoarthritis, implicating that other macrophage-derived mediators such as S100A8/A9 are responsible for the joint damage. References: van Lent et al. 2012 Acknowledgement: This research was supported by the Dutch Arthritis Association. Disclosure of Interest: None declared