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 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.
Han
Sang-Bae
SB
Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oundong, Yusong, Taejon 305-333, South Korea.
Lee
Chang Woo
CW
Yoon
Yeo Dae
YD
Kang
Jong Soon
JS
Lee
Ki Hoon
KH
Yoon
Won Kee
WK
Kim
Young Kook
YK
Lee
Kiho
K
Park
Song-Kyu
SK
Kim
Hwan Mook
HM
D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D001419:Bacteria / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011353:Prodigiosin / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013997:Time Factors
C508018:Il2ra protein, mouse; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D016572:Cyclosporine; D011353:Prodigiosin