Sang-Bae Han, Chang Woo Lee, Yeo Dae Yoon, Jong Soon Kang, Ki
Hoon Lee, Won Kee Yoon, Young Kook Kim, Kiho Lee, Song-Kyu Park,
Hwan Mook KimEffective prevention of lethal acute
graft-versus-host disease by combined immunosuppressive therapy
with prodigiosin and cyclosporine
Biochem Pharmacol. 2005 Nov 15;70 (10):1518-26
Korea Research Institute of Bioscience and Biotechnology (KRIBB),
52 Oundong, Yusong, Taejon 305-333, South Korea.
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. |
