STUDY OF PRO-INFLAMMATORY (TNF-ALPHA, IL-1-ALPHA, 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

Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-in flammatory (TNF-alpha, IL-1 alpha, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in paucia rticular and polyarticular juvenile chronic arthritis (JCA) patients d uring the active (n = 22) and inactive (n = 14) period in order to det ermine pathogenic mechanisms and correlations between cytokines and la boratory parameters showing disease activity. The erythrocyte sediment ation rate (ESR), serum C-reactive protein (CRP) and IgG concentration s were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral b lood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ acti ve T cells (22.5%) were found to be significantly increased. In the ac tive period of JCA, plasma TNF-alpha and IL-6 concentrations were sign ificantly 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-alpha and IL-1 alpha levels were extremely hig h 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-alpha con centrations. In conclusion, increased local production of pro-inflamma tory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokine s (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production wa s not suggested to be primarily involved in the pathogenesis. In addit ion, not only CRP and ESR values, but also plasma IL-6 and TNF-alpha c oncentrations may be used as markers of disease activity.