Abstract
Interleukin-6 (IL-6) is involved in the pathogenesis of various inflammatory diseases, like rheumatoid arthritis (RA). In the present study, we investigated the role of IL-6 in osteoarthritis (OA) patients and the effects of the stilbenoids monomethyl pinosylvin and pinosylvin on the expression of the cartilage matrix components aggrecan and collagen II and the inflammatory cytokine IL-6 in human OA chondrocytes. Synovial fluid and plasma samples were obtained from 100 patients with severe OA [BMI 29.7 (8.3) kg/m2, age 72 (14) years, median (IQR); 62/38 females/males] undergoing total knee replacement surgery. IL-6 and matrix metalloproteinase (MMP) concentrations in synovial fluid and plasma were measured by immunoassay. The effects of pinosylvin on the expression of IL-6, aggrecan, and collagen II were studied in primary cultures of human OA chondrocytes. IL-6 levels in synovial fluid from OA patients [119.8 (193.5) pg/mL, median (IQR)] were significantly increased as compared to the plasma levels [3.1 (2.7) pg/mL, median (IQR)] and IL-6 levels in synovial fluid were associated with MMPs and radiographic disease severity. Natural stilbenoids monomethyl pinosylvin and pinosylvin increased aggrecan expression and suppressed IL-6 production in OA chondrocytes. The results propose that IL-6 is produced within OA joints and has an important role in the pathogenesis of OA. Stilbenoid compounds monomethyl pinosylvin and pinosylvin appeared to have disease-modifying potential in OA chondrocytes.
Highlights
Interleukin-6 (IL-6) was cloned in 1980s and it was first shown to promote the activation of T andB lymphocytes as well as to regulate the inflammation-associated acute-phase response
IL-6 concentrations in OA patients were comparable to those reported in healthy individuals [2]
It was shown that IL-6 correlated positively with and radiographic severity of OA; while plasma concentrations in synovial fluid were considerably higher in patients with cartilage defect or OA than in IL-6 concentrations
Summary
Interleukin-6 (IL-6) was cloned in 1980s and it was first shown to promote the activation of T and. B lymphocytes as well as to regulate the inflammation-associated acute-phase response. IL-6 is known as a mediator of inflammation, immune response and hematopoiesis [1]. Targeting IL-6 has become important in the drug development because of the pathological role of IL-6 in numerous adverse conditions. Tocilizumab which is a humanized monoclonal antibody against IL-6 receptor, is used as a second-line treatment of rheumatoid arthritis (RA). Osteoarthritis (OA) is the most common form of arthritis. The etiology of OA is still largely unknown risk factors like certain genes, gender, age, joint trauma and obesity have been identified. There are no effective disease-modifying treatments except surgical interventions and the treatment is mainly limited to analgesics and other symptomatic approaches [2,3]
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