© 1994 British Society for Rheumatology
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CIRCULATING CONCENTRATIONS AND PRODUCTION OF CYTOKINES AND SOLUBLE RECEPTORS IN RHEUMATOID ARTHRITIS PATIENTS: EFFECTS OF A SINGLE DOSE METHOTREXATE
*Department of Rheumatology University Hospital Higmegen The Netherlands
Department of Internal Medicine, University Hospital Nijmegen The Netherlands
F.Hoffmann-la-Roche CH-4002 Basel, Switzerland
Correspondence to:
P. Barrera, Department of Rheumatology, University Hospital Nijmegan, The Netherlands.
Methotrexate (MTX) is an effective treatment for RA and its effects may be partly due to cytokine modulation. Herein, we assessed the effects of a single MTX dose on the production and circulating concentrations of several cytokines and soluble receptors in 42 RA patients on three consecutive days. Three patient groups were studied: (a) 16 patients taking the first MTX dose, (b) 11 patients on chronic MTX treatment and (c) a control group of 15 patients not treated with MTX. Cytokine production was studied in peripheral blood mononuclear cells (PBMNC) and in a whole-blood culture system (WBCS). Group (a) had a more active disease according to laboratory parameters as well as higher circulating IL-6 levels (P = 0.002). The secretion of IL-ß by stimulated PBMNC (P = 0.008) was higher in this group and decreased significantly (P = 0.03) after a single MTX dose. No significant change in any parameter was observed after MTX in group (b). In the total patient group, circulating concentrations of IL-1ß and TNF-
were low but blood cells showed a high capacity of production for these cytokines. In contrast for sTNFRs, high circulating levels but a limited in vitro production were observed.
In conclusion, a single MTX dose may result in decreased production of IL-1ß by PBMNC in patients with active RA. Furthermore, we observed an imbalance in the production of TNF- and sTNFRs by peripheral blood cells of RA patients and propose that the WBCS is convenient for studying cytokine production in RA.
KEY WORDS: Cytokines, Soluble TNF receptors, Methotrexate, Rheumatoid arthritis
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