Study of pro-inflammatory (TNF-α, IL-1α, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: Correlations with clinical and laboratory parameters
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Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-α, IL-1α, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active (n=22) and inactive (n=14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF-α and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF-α and IL-1α levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF-α concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF-α concentrations may be used as markers of disease activity.
KeywordsAcute phase response Interleukins 1α, 2, 4, and 6 Juvenile chronic arthritis Tumour necrosis factor α
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- 2.Wood PHN. Special meeting on nomenclature and classification of arthritis in children. In: Munther M, editor. The care of rheumatic children. Basel: EULAR, 1978.Google Scholar
- 4.Schaller JG. Juvenile rheumatoid arthritis. In Behrman RE, Kliegmon RM, Nelson WE, Vaughan VC, editors. Nelson textbook of pediatrics, 14th edn. Philadelphia: WB Saunders, 1992:612–21.Google Scholar
- 5.Fye KH, Sack KH. Rheumatic Diseases. In: Stites DP, Terr AL, editors, 7th ed. Basic and Clinical Immunology. London: Appleton & Lange, 1991:438–64.Google Scholar
- 6.Emery P, Luqmani R. The validity of surrogate markers in rheumatic disease. Br J Rheumatol 1993;32(suppl 3):3–8.Google Scholar
- 9.Henderson B, Pettipher ER. Arthritogenic actions of recombinant IL-1 and tumor necrosis factor alpha in the rabbit: evidence for synergistic interactions between cytokines in vivo. Clin Exp Rheumatol 1989;75:306–10.Google Scholar
- 14.Miuller K, Hansen MB, Zak M, Nielsen S, Pedersen FK, de Nully P, Bendtzen K. Autoantibodies to IL-1a in sera from umblical cords, children and adults and from patients with juvenile chronic arthritis. Scand J Rheumatol 1996;25:64–7.Google Scholar
- 16.Venables P. Rheumatoid arthritis and other joint diseases. In: Brostoff J, Scadding GK, Male D, Roitt IM, editors. 1st ed. Clinical Immunology, Hong Kong, Gower Medical, 1991;5.1–5.15.Google Scholar
- 19.Miossec P. Pro- and antiinflammatory cytokine balance in rheumatoid arthritis. Clin Exp Rheumatol 1995;13(suppl 12):S13–S16.Google Scholar
- 22.Lipnick RN, Tsokos GC, Magilavy DB. Immune abnormalities in the pathogenesis of juvenile rheumatoid arthritis. Rheum Dis Clin North Am 1991;7:843–59.Google Scholar
- 23.Zvaifler NJ. Current concepts of pathogenesis of joint destruction in rheumatoid arthritis. Rheumatology in Europe 1995;suppl 2:151–67.Google Scholar