Effective prevention of lethal acute graft-versus-host disease by combined immunosuppressive therapy with prodigiosin and cyclosporine A

Prodigiosin (PDG), a bacterial metabolite, is a known T cell-specific immunosuppressant. Here, we compared its inhibitory potency and mode of action with cyclosporine A (CsA) in a mouse model. PDG efficiently inhibited T cell proliferation with an IC50 of 3.37 ng/ml, a similar dose to that of CsA (IC50 of 2.71 ng/ml). PDG inhibited only 11-2R alpha expression, but not IL-2 expression, whereas CsA inhibited both. Exogenously added IL-2 reversed the suppressive activity of CsA, but not that of PDG. Moreover, although both PDG and CsA markedly reduced mortality rates in lethal acute graft-versus-host disease (GVHD), the combined treatment was more effective than either drug alone. These results demonstrate that PDG and CsA have similar inhibitory potencies, but different modes of action, and suggest that PDG has potential use as a supplementary immunosuppressant in combination with CsA for the treatment of GVHD. (c) 2005 Elsevier Inc. All rights reserved.