title: Circulating concentrations and production of cytokines and soluble receptors in rheumatoid arthritis patients: effects of a single dose methotrexate.
abstract: 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-1 beta 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-1 beta and TNF-alpha 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-1 beta by PBMNC in patients with active RA. Furthermore, we observed an imbalance in the production of TNF-alpha and sTNFRs by peripheral blood cells of RA patients and propose that the WBCS is convenient for studying cytokine production in RA.
authors.affiliation: Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Barrera
authors.forename: A M
authors.initials: AM
authors.lastname: Boerbooms
authors.forename: P N
authors.initials: PN
authors.lastname: Demacker
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
authors.forename: H
authors.initials: H
authors.lastname: Gallati
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009994:Osmolar Concentration; D018121:Receptors, Cytokine / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D008727:Methotrexate