Differences in the effects of the antirheumatic drugs, bucillamine and D-penicillamine, on mitogen-induced proliferation of mouse spleen cells.

The effect of bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine], a new antirheumatic drug, on the concanavalin A (Con A)-induced proliferation of mouse spleen cells was compared with the effect of D-penicillamine (D-pen). Bucillamine inhibited the Con A-induced incorporation of thymidine (TdR) into mouse spleen cells in a dose-dependent fashion. At the concentration of 10(-4) M, bucillamine inhibited the incorporation by approximately 80%. The inhibitory effect of bucillamine was not enhanced by the addition of copper. In contrast, D-pen showed the same degree of inhibition only in the presence of copper. (4R)-7,7-Dimethyl-6-oxo-tetrahydro-3H-1,2,5-dithiazepine-4-carboxy lic acid (SA981), an intramolecular disulfide derivative of bucillamine, also showed the same degree of inhibition as bucillamine in the absence and presence of copper, whereas D-penicillamine disulfide did not show the inhibitory effect even in the presence of copper. The inhibitory effects of bucillamine and SA981 were not abolished significantly by the addition of catalase which restored the inhibition by D-pen plus copper. The mechanism of inhibition by D-pen plus copper is believed to involve the production of hydrogen peroxide resulting from the oxidation of D-pen. The results in this study, however, indicated that the inhibitory effect of bucillamine is not due to the production of hydrogen peroxide.