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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Animals
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Arthritis, Experimental / drug therapy
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Arthritis, Experimental / etiology
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Arthritis, Experimental / prevention & control
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Bacteria / chemistry
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Bacteria / immunology
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Bacteria / metabolism
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Cell Proliferation / drug effects
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Cyclosporine / immunology
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Cyclosporine / pharmacology
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Cyclosporine / therapeutic use*
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Disease Models, Animal
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Drug Administration Schedule
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Drug Evaluation, Preclinical / methods
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Drug Therapy, Combination*
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Female
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Graft vs Host Disease / drug therapy
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Graft vs Host Disease / etiology
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Graft vs Host Disease / prevention & control*
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Immunosuppressive Agents / immunology
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Immunosuppressive Agents / pharmacology
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Immunosuppressive Agents / therapeutic use*
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / genetics
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Interleukin-2 / immunology
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Interleukin-2 Receptor alpha Subunit
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Lymphocytes / drug effects
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Prodigiosin / immunology
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Prodigiosin / pharmacology
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Prodigiosin / therapeutic use*
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Receptors, Interleukin / antagonists & inhibitors
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Receptors, Interleukin / genetics
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Receptors, Interleukin / immunology
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T-Cell Antigen Receptor Specificity / immunology
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Time Factors
Substances
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Il2ra protein, mouse
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Immunosuppressive Agents
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Receptors, Interleukin
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Cyclosporine
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Prodigiosin