© 1995 British Society for Rheumatology
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EFFECT OF METHOTREXATE ALONE OR IN COMBINATION WITH SULPHASALAZINE ON THE PRODUCTION AND CIRCULATING CONCENTRATIONS OF CYTOKINES AND THEIR ANTAGONISTS. LONGITUDINAL EVALUATION IN PATIENTS WITH RHEUMATOID ARTHRITIS
,
*Department of Rheumatology, University Hospital and University of Nijmegen Nijmegen, The Netherlands
Department of Internal Medicine, University Hospital and University of Nijmegen Nijmegen, The Netherlands
Department of Medical Statistics, University Hospital and University of Nijmegen Nijmegen, The Netherlands
Correspondence to:
Correspondence to: P. Barrera, Department of Rheumatology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
In a recent study from our group, the combination of methotrexate and sulphasalazine (MTX + SASP) seemed superior to MTX alone in the treatment of rheumatoid arthritis (RA). To assess the impact of these therapies on the cytokine cascade, the in vitro production and circulating concentrations of several cytokines and endogenous cytokine antagonists were measured in 30 healthy controls and longitudinally in a subset of 26 patients enrolled in this study. Compared to controls, RA patients had significantly higher circulating concentrations of interleukin-6 (IL-6), soluble receptors for tumour necrosis factor (sTNFR), soluble receptors for interleukin-2 (sIL-2R) and interleukin-1 receptor antagonists (IL-1RA), and their peripheral blood mononuclear cells (PBMNC) showed a higher spontaneous production of interleukin- 1ß (IL-1ß), tumour necrosis factor 
(TNF) and IL-1RA (both secreted and cell-associated) and a higher stimulated production of cell-associated TNF, IL-1RA and (to a lesser extent) IL-1ß. Treatment withMTX alone (n = 12) or combined with SASP (n = 14), resulted in significant reductions of circulating IL-6 and sIL-2R but did not alter IL-1ß, TNF or IL-1RA concentrations. Decreases in circulating levels of sTNFR and in the in vitro production of cell-associated IL-1ß and IL-1RA after stimulation were only observed in patients treated with MTX + SASP. The concentrations of IL-1RA and sTNFR in the circulation exceeded moderately those of IL-1ß and TNF but this is probably insufficient to block IL-1 and TNF activity. In conclusion, therapy with MTX alone or with SASP modulates IL-6 and sIL-2R concentrations in RA. Decreased production of IL-1ß and IL-1RA and circulating sTNFR levels were only observed during therapy with MTX + SASP. Whether this relates to the better clinical effect observed with the combination therapy remains to be investigated. Circulating levels ofIL-6, sIL-2R and sTNFR seem useful markers of disease activity in RA.
KEY WORDS: Cytokines, Methotrexate, Sulphasalazine, Combination therapy
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