Comparative inhibitory effects of bucillamine and D-penicillamine on the function of human B cells and T cells.
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 (BUC-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-gamma (IFN gamma) production was induced in CD4+ T cells by stimulation with immobilized anti-CD3. RESULTS. BUC-ID suppressed IgM production induced 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 micrograms/ml) significantly suppressed IFN gamma 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 microgram/ml) significantly suppressed IgM production induced by SAC + IL-2, but not T cell IFN gamma 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.[1]References
- Comparative inhibitory effects of bucillamine and D-penicillamine on the function of human B cells and T cells. Hirohata, S., Lipsky, P.E. Arthritis Rheum. (1994) [Pubmed]
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