Gene therapy using interleukin 12 successfully treats GVHD in mice.
Since GVHD is characterized by the production of Th2 cytokines, and IL-12 is know to reduce TH2 activity, Tadanobu Okubo, PhD and co-investigators at Yokohama City University of Medicine in Japan theorized that gene therapy with IL-12 might affect the clinical manifestations of GVHD in mice models of the disease. The treatment groups received intramuscular injections every 3 weeks of varying doses of DNA plasmids that encode for IL-12.
The 100 mcg dose of IL-12 DNA "...prevented the development of both the immunological and clinical manifestations of chronic GVHD," Okubo and colleagues reported in the April 1 issue of the Journal of Immunology. IL-12 gene therapy also "...altered the balance between Th2 and Th1 cytokine production, suppressed hypergammaglobulinemia, and prevented the [kidney complications seen] in chronic GVHD." In contrast, the authors said administration of the plasmid encoding an IL-12 antagonist exacerbated GVHD.
The study is the first to demonstrate in an animal model that GVHD can be effectively treated with IL-12 gene therapy, and that this treatment does not induce acute GVHD, the researchers wrote. The findings, they said, support a critical role for IL-12 "...in determining the cytokine balance in GVHD," and suggest that gene therapy with IL-12 may be of benefit in a variety of human autoimmune disorders. The authors added that IL-12 gene therapy may offer significant advantages over current treatments for GVHD which rely on "...multiple daily injections of expensive cytokines."
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|Comment:||Gene therapy using interleukin 12 successfully treats GVHD in mice.|
|Date:||Jul 16, 1999|
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