Interleukin 17 Levels Are Increased in Juvenile Idiopathic Arthritis Synovial Fluid and Induce Synovial Fibroblasts to Produce Proinflammatory Cytokines and Matrix Metalloproteinases

SHILPI AGARWAL, RAMNATH MISRA, and AMITA AGGARWAL

ABSTRACT.

Objective. Cytokines are the major mediators of joint damage in chronic arthritis. Data on synovial fluid (SF) concentration of Th17 cell-derived cytokine interleukin 17 (IL-17) in patients with juvenile idiopathic arthritis (JIA) are sparse. We measured levels of IL-17 in SF specimens from children with enthesitis-related arthritis (ERA) and polyarticular JIA (poly-JIA), and studied the ability of IL-17 to produce matrix metalloproteinases (MMP) and cytokines by fibroblast-like synoviocytes (FLS) from patients with ERA.

Methods. IL-17 levels were measured in SF of patients with ERA (n = 43), poly-JIA (n = 17), rheumatoid arthritis (RA; n = 35), and osteoarthritis (OA; n = 10) by ELISA. In patients with JIA, 10 paired serum samples were also assayed. FLS were cultured from SF of patients with ERA and subsequently stimulated for 48 h by IL-17 or tumor necrosis factor-a. Later the production of IL-6, IL-8, MMP-1, MMP-3, and tissue inhibitor of metalloproteinase (TIMP)-1 was measured in the culture supernatants by ELISA.

Results. Median IL-17 levels in SF were higher in patients with JIA [28 pg/ml (range 0–200)] compared to OA [0 pg/ml (range 0–84); p < 0.001] and RA (p < 0.05). The levels were comparable between poly-JIA patients and the ERA group. The median SF IL-17 levels were significantly higher compared to serum levels in children with JIA (p < 0.005). In ERA, SF IL-17 correlated with number of swollen joints (r = 0.35; p < 0.05), number of joints with limited mobility (r = 0.55; p < 0.001), and number of tender joints (r = 0.46; p < 0.01); however, no correlation was seen with erythrocyte sedimentation rate. IL-17 induced FLS to produce IL-6, IL-8, MMP-3, and MMP-1. However, there was no effect on the production of TIMP.

Conclusion. Increased IL-17 levels in ERA SF correlate with disease activity and this may be due to increased production of MMP and cytokines by IL-17. (First Release Jan 15 2008; J Rheumatol 2008;35:515–9)

Key Indexing Terms:

CYTOKINES
JUVENILE RHEUMATOID ARTHRITIS
TH17 CELLS
INFLAMMATION

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From the Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Supported by a grant from the Indian Council of Medical Research, Government of India, to Dr. Aggarwal. Dr. Agarwal is supported by a fellowship from university grants commission.

S. Agarwal, MSc; R. Misra, MD; A. Aggarwal, MD, DM, Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.

Address reprint requests to Dr. A. Aggarwal, Additional Professor (Clinical Immunology), Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Accepted for publication October 16, 2007.

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