Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

Abstract

IntroductionThis study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.MethodsIL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogenous IL-6 and addition of IL-6, in a regeneration model and in osteoarthritic explants in the presence of synovial fluid, respectively. Readout parameters were DNA and glycosaminoglycan (GAG) content and release. Differences between controls and IL-6 blocked or supplemented samples were determined by univariate analysis of variance using a randomized block design.ResultsSynovial fluid of patients with symptomatic cartilage defects contained more IL-6 than synovial fluid of healthy donors (P = 0.001) and did not differ from osteoarthritic donors. IL-6 production of osteoarthritic chondrocytes during cartilage regeneration was higher than that of healthy and defect chondrocytes (P < 0.001). Adding IL-6 increased GAG production by healthy chondrocytes and decreased GAG release by osteoarthritic chondrocytes (P < 0.05). Inhibition of IL-6 present in osteoarthritic synovial fluid showed a trend towards decreased GAG content of the explants (P = 0.06).ConclusionsOur results support a modest anabolic role for IL-6 in cartilage matrix production. Targeting multiple cytokines, including IL-6, may be effective in improving cartilage repair in symptomatic cartilage defects and osteoarthritis.

α-Defensin as a predictor of periprosthetic shoulder infection

“…Patients undergoing primary shoulder arthroplasty were not used as controls because of inconsistency in the literature regarding alterations in synovial fluid biomarkers in osteoarthritis. 24,33 During surgery for this control group, intraoperative synovial fluid was obtained through an arthroscopic portal at the start of the procedure and sent for a-defensin analysis.…”

Association between -174G/C and -572G/C interleukin 6 gene polymorphisms and severe radiographic damage to the hands of Mexican patients with rheumatoid arthritis: a preliminary report

“…High IL-6 levels are observed in the serum and synovial tissue of patients with RA (Tsuchida et al, 2012). It has been observed that polymorphisms in the IL6 gene promoter region may be responsible for changes in the expression of IL-6 (Spoto et al, 2015), leading to an increase in the inflammatory process and the development of radiographic joint damage in hands.…”

Wear in human knees

“…IL-6 activity in synovial fluid in OA patients has been reported [18,120]. Elevated concentrations of IL-6 have been found in OA patients [113]. MMPs promote breakdown of cartilage and are involved in the progression of OA as MMPs are responsible for degradation process in OA cartilage [120].…”

“…Cytokines may play an important role in OA [113]. Some cytokines can inhibit production of the cartilage matrix and therefore influence the balance between synthesis and degradation of the tissue matrix [18].…”