The British Journal of Rheumatology, Vol 37, 502-508, Copyright © 1998 by British Society for Rheumatology
RJ Dolhain, PP Tak, BA Dijkmans, P De Kuiper, FC Breedveld and AM Miltenburg
Methotrexate (MTX) is one of the most widely prescribed drugs in the
treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts
its anti-rheumatic effect has not yet been defined. The aim of the present
study was to investigate the effect of MTX treatment (7.5- 15 mg/week) on
synovial tissue in RA. For this purpose, synovial biopsies were taken from
11 RA patients before and 16 weeks after initiation of MTX therapy.
Immunohistochemistry was performed using monoclonal antibodies (MAb)
specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon
gamma (IFN-gamma), interleukin (IL)- 1alpha, IL-1beta, tumour necrosis
factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for
disease activity improved during the period of treatment.
Immunohistochemical analysis revealed a statistically significant decrease
in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the
adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial
scores for inflammatory cells, monokines and adhesion molecules suggests
that the anti- inflammatory effect of MTX is, in part, dependent on a
reduction in monokine-inducible vascular adhesion molecules and subsequent
reduction of cell traffic into joints.
ORIGINAL PAPERS
Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
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