CELL-TYPE-SPECIFIC RESPONSE OF PERIPHERAL-BLOOD LYMPHOCYTES TO METHOTREXATE IN THE TREATMENT OF RHEUMATOID-ARTHRITIS

The mode of action of methotrexate in the treatment of rheumatoid arth ritis is still questionable. Although in vitro results suggest an immu nosuppressive effect of methotrexate, several clinical studies have fa iled to confirm these effects in patients treated with oral low-dose m ethotrexate. With respect to the highly variable bioavailability of me thotrexate, we investigated the effects of an intravenous administrati on of 15 mg methotrexate per week on peripheral blood lymphocyte subse ts in eight patients with rheumatoid arthritis. Methotrexate after 12 weeks significantly (P<0.01) reduced total peripheral blood lymphocyte s and led to a pronounced redistribution of lymphocyte subsets with a preferred reductive effect on B-lymphocytes (P<0.005) and T-lymphocyte s (P<0.05). Natural killer cells and killer cell-like T cells, on the other hand, were unaffected by the treatment. Our results suggest a ce ll-type specific effect of intravenously administered low-dose methotr exate on peripheral blood lymphocytes. This effect, in our opinion, ma y contribute to the mode of action of methotrexate as an immunosuppres sive drug in the treatment of rheumatoid arthritis.