Effects of certain antirheumatic drugs on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine.

The effects of antirheumatic drugs on in vitro responses of normal human peripheral blood lymphocytes were examined and found to affect phytomitogen, antigen, and mixed lymphocyte responses. The drugs and concentrations (mumg/ml) at which 50% inhibition (ID50) of phytomitogen stimulation occurred were acetylsalicylic acid, 80; phenylbutazone, 150; indomethacin, 250; sodium aurothiomalate, 200; hydroxychloroquine, 75; D-penicillamine, 400; hydrocortisone, 50; naproxen, 350; and sodium meclofenamate, 175. Acetaminophen enhanced blastogenesis by 100% at 200 mug/ml, but was 50% inhibitory at 500 mug/ml. Other drugs had no effects. Numbers of viable cells in cultures with and without mitogens and drugs were generally similar at beginnings and ends of experiments. Stimulated cell cultures containing combinations of drugs exhibited greater inhibition than did cultures of individual drugs. Inhibition by drugs was greater when cells were cultured in medium alone than in medium with 20% plasma. Cells exposed overnight to phenylbutazone, indomethacin, sodium aurothiomalate, or sodium meclofenamate, then washed and stimulated, responded generally as well as did cells not exposed to drugs. Because some of these drugs exhibited effects at concentrations approaching therapeutic levels, these findings may be pertinent to clinical investigations of cellular immune responses of patients on drug therapy and to possible mechanisms of action for certain drugs.