Inhibition of mitogen-induced response of human peripheral blood mononuclear cells by bucillamine, a new antirheumatic sulfhydryl drug
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The mechanism of action of bucillamine, [N-(2-mercapto-2-methylpropionyl)-l-cysteine] (BC), a novel antirheumatic drug that is used in patients with rheumatoid arthritis (RA), was compared with that of d-penicillamine (DP). BC inhibited phytohemagglutinin (PHA)-induced DNA synthesis 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 cupric ions. Significant inhibition of DNA synthesis was observed at a BC concentration of 10 μg/ml. The disulfide form of BC, but not DP disulfide, suppressed the proliferation of PBMCs. After preincubation of human peripheral blood T lymphocytes or Møs with BC or DP, these cells were combined and the overall PHA response was estimated. Inhibition of the PHA response was observed following pretreatment of either T lymphocytes or Møs with BC, whereas inhibition was attained only when T lymphocytes were pretreated with DP and copper. As sulfhydryl agents produce hydrogen peroxide in the presence of cupric ions, the effect of catalase on DP- and BC-induced inhibition of PBMC DNA synthesis was examined. Catalase partially reversed the BC-induced inhibition of DNA synthesis of PBMCs, and it restored the inhibition by DP and copper almost to the control level. These results suggest that BC suppresses the function of both T lymphocytes and Møs in the mitogen response of PBMCs, whereas the action of DP is targeted at T lymphocytes.
Key wordsBucillamine d-Penicillamine Hydrogen peroxide Cupric ion Rheumatoid arthritis
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