Immunosuppressive activity of streptonigrin in vitro and in vivo.

The immune system is composed of various cells with distinct functions. Thus, highly selective immunomodulators are necessary for artificial regulation of immune reactions. We screened microbial products for such immunomodulators and we identified streptonigrin as a selective suppressor of B-cell proliferation induced by lipopolysaccharide. Streptonigrin directly suppressed the late phase of proliferation of B-cells. The inhibition of topoisomerase II was implicated as the mechanism of the B-cell-selective suppression. In cultured cell lines, however, streptonigrin preferentially suppressed the growth of an interleukin-3-dependent myeloid cell line rather than B-cell lines. In addition, the treatment with streptonigrin in vivo suppressed T-cells more significantly than B-cells and dramatically reduced the spleen weight. These results suggest that streptonigrin preferentially suppresses myeloid T-cell precursors in vivo.