Immunomodulating properties of prodigiosin 25-C, an antibiotic which preferentially suppresses induction of cytotoxic T cells.
An antibiotic, prodigiosin 25-C, preferentially suppresses cytotoxic T lymphocytes (CTL) without affecting antibody production. Here, we investigated the effect of prodigiosin 25-C on delayed-type hypersensitivity (DTH), graft versus host reaction (GvHR) and allogeneic skin graft rejection. DTH reactions were markedly inhibited by ip treatment of the mice with prodigiosin 25-C. Cell transfer experiments indicated that prodigiosin 25-C exerted its suppressive effect on the late efferent phase rather than on the induction phase of DTH. Prodigiosin 25-C suppressed induction of anti-host CTL when GvHR was induced by iv inoculating splenocytes of parental C57BL/6 mice to adult unirradiated BDF1 mice. It had little effect on GvHR-induced splenomegaly observed 2 weeks after the inoculation, but significantly delayed the subsidence of splenomegaly as revealed 8 weeks later, suggesting that suppression of CTL converts immunosuppressive GvHR to immunostimulative one as reported by G. M. Shearer. However, reduction of interleukin-2 (IL-2) production and mitogen responses induced by GvHR were not rescued by prodigiosin 25-C treatment. Prodigiosin 25-C moderately prolonged survival of major histocompatibility (MHC)-mismatched skin grafts. Since the mode of action of prodigiosin 25-C is distinct from those of cyclosporin A and FK506, these results demonstrate potential usefulness of the antibiotic for a supplementary immunosuppressant.
Tsuji
R F
RF
Department of Agricultural Chemistry, University of Tokyo, Japan.
Magae
J
J
Yamashita
M
M
Nagai
K
K
Yamasaki
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005260:Female; D006087:Graft vs Host Reaction / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; C077331:prodigiosin 25C; D011353:Prodigiosin