INHIBITION OF MITOGEN-INDUCED RESPONSE OF HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS BY BUCILLAMINE, A NEW ANTIRHEUMATIC SULFHYDRYL DRUG

The mechanism of action of bucillamine, [N-(2-mercapto-2-methylpropion yl)-L-CySteine] (BC), a novel antirheumatic drug that is used in patie nts with rheumatoid arthritis (RA), was compared with that of D-penici llamine (DP). BC inhibited phytohemagglutinin (PHA)-induced DNA synthe sis of peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, and this inhibition occurred both in the presence and absence of copper, whereas DP-induced inhibition required the presence of cupr ic ions. Significant inhibition of DNA synthesis was observed at a BC concentration of 10 mug/ml. The disulfide form of BC, but not DP disul fide, suppressed the proliferation of PBMCs. After preincubation of hu man peripheral blood T lymphocytes or Mos with BC or DP, these cells w ere combined and the overall PHA response was estimated. Inhibition of the PHA response was observed following pretreatment of either T lymp hocytes or Mos with BC, whereas inhibition was attained only when T ly mphocytes were pretreated with DP and copper. As sulfhydryl agents pro duce hydrogen peroxide in the presence of cupric ions, the effect of c atalase on DP- and BC-induced inhibition of PBMC DNA synthesis was exa mined. Catalase partially reversed the BC-induced inhibition of DNA sy nthesis of PBMCs, and it restored the inhibition by DP and copper almo st to the control level. These results suggest that BC suppresses the function of both T lymphocytes and Mos in the mitogen response of PBMC s, whereas the action of DP is targeted at T lymphocytes.