Purpose: Interleukin-17 (IL-17) is an important factor in the pathogenesis of autoimmune diseases and allergy, and IL-17 antagonists are currently evaluated in randomized trials with encouraging results. In OA IL-17 contributes to cartilage breakdown and synovial infiltration by inducing the release of chemokines by chondrocytes and synovial fibroblasts independent of the IL-1 and TNF-alpha pathway. It also affects cartilage matrix turnover, induces angiogenesis in articular tissue, and amplifies joint inflammation. However, IL-17 is only infrequently detected in OA and clinical studies are sparse. We aimed at evaluating the relation between absence or presence of IL- 17 in synovial fluid (SF) of patients with endstage knee and hip OA and (1) other (adipo-)cytokine SF concentrations, and (2) clinical and radiographic disease parameters. Methods: Cross-sectional study including patients prior to total hip (THA) and knee arthroplasty (TKA) operated upon for primary OA at a large tertiary hospital between January and December 2010. The morning of surgery concentrations of IL-17, IL-6, leptin, visfatin, adiponectin, resistin, MCP-1, MCP-3 and NGF were sampled from synovial fluid and assessed using ELISA kits. Baseline characteristics recorded preoperatively included age, sex, BMI, co-morbidities, pain and function (WOMAC), and radiographic analyses (OA features, K&L grade, minimal JSW). Results: 152 patients were included, 68 prior to THA and 84 to TKA. Mean age was 73 (+/-9) years, 64% were women. In 14 patients (9.2%) IL- 17was present in the SF (median concentration 7.9 pg/ml, IQR 1.6; 20.6). These patients had significantly higher median SF concentrations of IL- 6, leptin, resistin, MCP-3 and beta-NGF, and a tendency to be female, younger, and obese class II, as compared to those without IL-17. Radiographic analyses revealed a significantly reduced min JSW together with a lower proportion of sclerosis and osteophytes in the presence of IL-17 in SF. No differences were found with respect to pain, function and comorbidities. There was a moderate correlation between Il-17 concentrations in SF and serum (r=0.482). Conclusions: The presence of IL-17 in SF of patients with primary end stage OA was associated with high levels of several other proinflammatory adipokines, cytokines and chemokines, and with a different radiographic OA feature pattern. Moreover, patients tended to be younger, more often women and obese class II. Our results may indicate a different OA phenotype with a potential for a new treatment option.
Lubbeke, A., Bas, S., Puskas, G. J., Suva, D., Finckh, A., Gabay, C., & Hoffmeyer, P. (2015). Presence of interleukin-17 in osteoarthritis: Does it indicate a different osteoarthritis phenotype. Osteoarthritis and Cartilage, 23, A321. https://doi.org/10.1016/j.joca.2015.02.582