Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Methotrexate (MTX) is one of the most widely prescribed drugs in thetreatment of rheumatoid arthritis (RA). The mechanism by which MTX exertsits anti-rheumatic effect has not yet been defined. The aim of the presentstudy was to investigate the effect of MTX treatment (7.5- 15 mg/week) onsynovial tissue in RA. For this purpose, synovial biopsies were taken from11 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, interferongamma (IFN-gamma), interleukin (IL)- 1alpha, IL-1beta, tumour necrosisfactor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters fordisease activity improved during the period of treatment.Immunohistochemical analysis revealed a statistically significant decreasein scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and theadhesion molecules E-selectin and VCAM-1. The observed decrease in synovialscores for inflammatory cells, monokines and adhesion molecules suggeststhat the anti- inflammatory effect of MTX is, in part, dependent on areduction in monokine-inducible vascular adhesion molecules and subsequentreduction of cell traffic into joints.