title: The effect of methotrexate (MTX) on expression of signalling lymphocytic activation molecule (SLAM) in patients with rheumatoid arthritis (RA) and its role in the regulation of cytokine production.
abstract: OBJECTIVE
  To investigate the effect of methotrexate (MTX) on cytokine production by activated CD4+ T-cells in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  The effect of MTX on intracellular expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), and cell surface expression of signalling lymphocytic activation molecule (SLAM) from freshly isolated peripheral blood mononuclear cells (PBMCs), and after in vitro culture with or without MTX, was analysed with flow cytometry in 18 patients with RA and 20 healthy controls.
  
  
  RESULTS
  Intracellular expression of IFN-gamma and IL-4 on freshly isolated CD4+ T-cells was significantly higher in patients with RA than in the controls (p<0.05). Intracellular expression of both IFN-gamma and IL-4 after culture with MTX was significantly lower than those after culture without MTX in patients with RA. Although no significant difference was observed in SLAM expression on freshly isolated CD4+ T-cells between patients with RA and the controls, MTX significantly decreased SLAM expression on both activated IFN-gamma+ and IL-4+CD4+ T-cells in patients with RA.
  
  
  CONCLUSIONS
  In vitro modulation of the cytokine network by MTX, IFN-gamma, and IL-4 is one of the major targets for MTX, and production of IFN-gamma and IL-4 by PBMCs may be suppressed by SLAM on activated CD4+ T-cell in patients with RA.
authors.affiliation: Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. y-morita@med.juntendo.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Fukazawa
authors.forename: M
authors.initials: M
authors.lastname: Hirashima
authors.forename: K
authors.initials: K
authors.lastname: Kaga
authors.forename: M
authors.initials: M
authors.lastname: Kusaoi
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Touyama
authors.forename: K
authors.initials: K
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Takasaki
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000187:drug effects*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000187:drug effects*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*
chemical_list: D015703:Antigens, CD; D018501:Antirheumatic Agents; D016207:Cytokines; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D015847:Interleukin-4; D007371:Interferon-gamma; D008727:Methotrexate