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Publication : Administration of an IL-12-encoding DNA plasmid prevents the development of chronic graft-versus-host disease (GVHD).

First Author  Okubo T Year  1999
Journal  J Immunol Volume  162
Issue  7 Pages  4013-7
PubMed ID  10201922 Mgi Jnum  J:54283
Mgi Id  MGI:1334884 Doi  10.4049/jimmunol.162.7.4013
Citation  Okubo T, et al. (1999) Administration of an IL-12-encoding DNA plasmid prevents the development of chronic graft-versus-host disease (GVHD). J Immunol 162(7):4013-7
abstractText  The transfer of DBA/2 spleen cells into (C57BL/10 x DBA/2)F1 mice induces chronic graft-vs-host disease (GVHD), which is characterized by the production of Th2 cytokines, hypergamma-globulinemia, and immune complex-mediated glomerulonephritis like systemic lupus erythematosus. IL-12 strongly induces the production of Th1 cytokines and reduces Th2 activity in vivo. In this study, the effect of gene therapy on the development of murine chronic GVHD was examined using an IL-12-encoding plasmid (pCAGGSIL-12), with the expectation that it might regulate Th1/Th2 activity and have a beneficial impact on the clinical manifestations of disease. pCAGGSIL-12 or its p40 antagonist plasmid (pCAGGSp40) were injected i.m. every 3 wk in GVHD-induced (C57BL/10 x DBA/2)F1 mice. A total of 100 microg of pCAGGSIL-12 improved the Th1/Th2 balance in vivo, suppressed the production of IgG, and significantly reduced the development of glomerulonephritis. GVHD was exacerbated by injection of the pCAGGSp40 antagonist. Our results demonstrate that GVHD can be treated successfully by the administration of an IL-12-encoding plasmid, and that such therapy does not induce acute GVHD.
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