CIRCULATING CONCENTRATIONS AND PRODUCTION OF CYTOKINES AND SOLUBLE RECEPTORS IN RHEUMATOID-ARTHRITIS PATIENTS - EFFECTS OF A SINGLE-DOSE METHOTREXATE

Methotrexate (MTX) is an effective treatment for RA and its effects ma y be partly due to cytokine modulation. Herein, we assessed the effect s of a single MTX dose on the production and circulating concentration s of several cytokines and soluble receptors in 42 RA patients on thre e consecutive days. Three patient groups were studied: (a) 16 patients taking the first MTX dose, (b) 11 patients on chronic MTX treatment a nd (c) a control group of 15 patients not treated with MTX. Cytokine p roduction was studied in peripheral blood mononuclear cells (PBMNC) an d in a whole-blood culture system (WBCS). Group (a) had a more active disease according to laboratory parameters as well as higher circulati ng IL-6 levels (P = 0.002). The secretion of IL-1beta by stimulated PB MNC (P = 0.008) was higher in this group and decreased significantly ( P = 0.03) after a single MTX dose. No significant change in any parame ter was observed after MTX in group (b). In the total patient group, c irculating concentrations of IL-1beta and TNF-alpha were low but blood cells showed a high capacity of production for these cytokines. In co ntrast for sTNFRs, high circulating levels but a limited in vitro prod uction were observed. In conclusion, a single MTX dose may result in d ecreased production of IL-1beta by PBMNC in patients with active RA. F urthermore, we observed an imbalance in the production of TNF-alpha an d sTNFRs by peripheral blood cells of RA patients and propose that the WBCS is convenient for studying cytokine production in RA.