Suppressive influences of methotrexate on the generation of CD14(+) monocyte-lineage cells from bone marrow of patients with rheumatoid arthritis

An adequate supply of peripheral blood monocytes, granulocytes, and platele ts is necessary for an optimal inflammatory process. We have previously dem onstrated that the generation of CD14 (+) monocyte lineage cells from the b one marrow is accelerated in patients with rheumatoid arthritis (RA). The c urrent studies examined the influences of methotrexate (MTX), a potent dise ase modifying antirheumatic drug (DMARD), on the capacity of bone marrow pr ogenitor cells to generate CD14 (+) cells in patients with RA, in order to delineate its mechanism of action. CD14 (-) cells purified from bone marrow specimens of 14 patients with active RA were cultured in the presence or t he absence of pharmacologically attainable concentrations of MTX (0.2 mu M) . After incubation for 14 days, the cells were analyzed by how cytometry fo r expression of CD14 and HLA-DR. The generation of CD14 (+) cells from RA b one marrow CD14 (-) progenitor cells was significantly suppressed by MTX Ho wever, the expression of HLA-DR on bone marrow-derived CD14 (+) cells was n ot significantly influenced by MTX. There was no significant difference in the effect of MTX on the generation of CD14 (+) cells between patients with prednisolone and those without prednisolone. The production of IL-12 in bo ne marrow cell cultures was not inhibited, but was rather enhanced, by MTX, suggesting that the suppression of the generation of CD14 (+) cells might not be due to the inhibition of cytokine production. The results are consis tent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, th e data suggest that the generation of CD14 (+) cells and the expression of HLA-DB on such marrow-derived CD14 (+) cells are regulated by different mec hanisms. (C) 1999 Academic Press.