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.

Highlights

  • Osteoarthritis (OA) is the most common of the arthritic diseases causing pain and disability for sufferers

  • Osteophytes, sclerosis and minimum joint space width were significantly reduced in patients with detectable IL17 in synovial fluid

  • The presence of IL-17 in the synovial fluid identifies a substantial subset of primary end-stage OA patients with distinct biological and clinical features

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Summary

Introduction

Osteoarthritis (OA) is the most common of the arthritic diseases causing pain and disability for sufferers. The disease is characterized by loss of articular cartilage and formation of osteophytes with synovial inflammation (synovitis) present in a significant proportion of patients. Long-regarded as a non-inflammatory, degenerative disease, recent research consistently identifies a role of inflammation in driving both OA initiation and progression.[1, 2] A further shift in the OA disease paradigm is its consideration not as a single disease but instead as a series of different joint disorders that converge upon the common characteristic of articular cartilage loss in the absence of other pathology such as rheumatoid arthritis. Individuals with OA show heterogeneity in clinical features including pain, speed of disease progression, bony changes (osteophyte formation, sclerosis of subchondral bone), synovitis and functional scores. This hinders prognostic, diagnostic and therapeutic advances, and treatments are limited to analgesia and arthroplasty. Adipocytokines and inflammatory cytokines are produced by adipocytes and inflammatory cells, which are present in both joint-resident and systemic adipose tissue.[6, 7] The presence of inflammatory cytokines and adipokines in OA SF is in agreement with both inflammatory and metabolic or obesity-related risk factors as key drivers of OA

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