Presence of IL-17 in synovial fluid identifies a potential inflammatory osteoarthritic phenotype

Abstract

PurposeOsteoarthritis (OA) is a common and heterogeneous arthritic disorder. Patients suffer pain and their joints are characterized by articular cartilage loss and osteophyte formation. Risk factors for OA include age and obesity with inflammation identified as a key mediator of disease pathogenesis. Interleukin-17A (IL-17) is a pro-inflammatory cytokine that has been implicated in inflammatory diseases such as rheumatoid arthritis. IL-17 can upregulate expression of inflammatory cytokines and adipocytokines. The aim of this study was to evaluate IL-17 levels in the synovial fluid of patients with end-stage knee and hip OA in relation to inflammation- and pain-related cytokines and adipocytokines in synovial fluid and serum, and clinical and radiographic disease parameters.MethodsThis is a cross-sectional study of 152 patients undergoing total hip and knee arthroplasty for OA. IL-17, IL-6, leptin, adiponectin, visfatin, resistin, C-C Motif Chemokine Ligand 2 (CCL2), C-C Motif Chemokine Ligand 7 (CCL7) and nerve growth factor (NGF) protein levels were measured in synovial fluid and serum using enzyme-linked immunosorbent assay (ELISA). Baseline characteristics included age, sex, body mass index, co-morbidities, pain and function, and radiographic analyses (OA features, K&L grade, minimal joint space width).Results14 patients (9.2%) had detectable IL-17 in synovial fluid. These patients had significantly higher median concentrations of IL-6, leptin, resistin, CCL7 and NGF. Osteophytes, sclerosis and minimum joint space width were significantly reduced in patients with detectable IL-17 in synovial fluid. No differences were found in pain, function and comorbidities. IL-17 concentrations in synovial fluid and serum were moderately correlated (r = 0.482).ConclusionThe presence of IL-17 in the synovial fluid therefore identifies a substantial subset of primary end-stage OA patients with distinct biological and clinical features. Stratification of patients on the basis of IL-17 may identify those responsive to therapeutic targeting.

The Role of Inflammation in the Pathogenesis of Osteoarthritis

“…Other than that, IL-17 promotes the recruitment and activation of neutrophils, which are the initial cell types recruited to the inflammation sites [40]. Activated neutrophils synthesize 2 [41]. Increased IL-17 and IL-22 levels are also detected in the synovial fluid of temporomandibular joint of patients with osteoarthritis [42].…”

“…The study suggested Mediators of Inflammation that CCL2 is secreted by injured chondrocytes and synovial fibroblasts and it recruits CCR2-expressing monocytes to the damaged tissues. CCL7 is a monocyte chemoattractant, which has been shown to increase in the synovial fluid of patients with osteoarthritis [41]. Production of CCL7 from synoviocytes is enhanced by IL-17 [41].…”

“…CCL7 is a monocyte chemoattractant, which has been shown to increase in the synovial fluid of patients with osteoarthritis [41]. Production of CCL7 from synoviocytes is enhanced by IL-17 [41]. Patients with facet joint osteoarthritis (n = 48) also demonstrated elevated CCL4 and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) compared to healthy controls (n = 10) [64].…”

<p>Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model</p>

“…[78][79][80] There is evidence that high numbers of fibroblasts in knee synovium can prompt inflammation due to overexpression of TGF-β. 81,82 BSP is usually located in the ECM of bone and involved in the primary bone formation during embryonic development. 83 It could be shown that BSP stimulated osteoblast differentiation, bone growth and vascularization in murine calvarial defect models.…”

Adipose Tissue is a Critical Regulator of Osteoarthritis

“…Several studies have demonstrated that IL-17 contributed to OA pathogenesis (26). Ultimately IL-17 could be a key factor contributing to the restoration of OA susceptibility in LD mice upon fat transplant, as others have reported IL-17 as a potential biomarker for a distinct subset of inflammatory OA patients with end stage disease (36).…”