Effective prevention of lethal acute graft-versus-host disease by combined immunosuppressive therapy with prodigiosin and cyclosporine A |
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Authors: | Han Sang-Bae Lee Chang Woo Yoon Yeo Dae Kang Jong Soon Lee Ki Hoon Yoon Won Kee Kim Young Kook Lee Kiho Park Song-Kyu Kim Hwan Mook |
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Affiliation: | Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oundong, Yusong, Taejon 305-333, South Korea. |
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Abstract: | 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 IC(50) of 3.37 ng/ml, a similar dose to that of CsA (IC(50) of 2.71 ng/ml). PDG inhibited only IL-2Ralpha 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. |
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Keywords: | Prodigiosin Cyclosporin A Graft-versus-host disease |
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