Comparative inhibitory effects of bucillamine and d‐penicillamine on the function of human b cells and t cells

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Abstract
Objective. Clinical trials have suggested that the efficacy of bucillamine (BUC) in rheumatoid arthritis (RA) may be superior to that of D‐penicillamine (DP), although the basis of the differences remains unclear. Previous studies have revealed that BUC has unique immunomodulatory effects that depend upon its capacity to form an intramolecular disulfide (BUG‐ID). We therefore examined the effects of BUC‐ID on the in vitro function of human B cells and T cells compared with those of DP, at their pharmacologically attainable concentrations. Methods. IgM production was induced in highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus interleukin‐2 (IL‐2) or with immobilized anti‐CD3–activated CD4+ T cells. Interferon‐γ (IFNγ) production was induced in CD4+ T cells by stimulation with immobilized anti‐CD3. Results. BUC‐ID suppressed IgM production iduced by SAC + IL‐2 as well as that induced by immobilized anti‐CD3–activated CD4+ T cells, whereas DP suppressed the latter more markedly than the former. DP (3 μg/ml) significantly suppressed IFNγ production by immobilized anti‐CD3–stimulated CD4+ T cells, but not IgM production induced by SAC + IL‐2 stimulation. By contrast, BUC‐ID (0.3 μg/ml) significantly suppressed IgM production induced by SAC + IL‐2, but not T cell IFNγ production. Of note, BUC‐ID did not suppress IL‐6 production by SAC‐activated B cells. Conclusion. These results indicate that the target cells of BUC and DP in vivo might be different, with the former inhibiting the function of B cells and the latter that of T cells. The data suggest the possibility that BUC may have a different effect in RA patients compared with the effect of DP, and may be effective in patients who do not respond to DP.