PROLONGATION OF LIVER ALLOGRAFT SURVIVAL AFTER INTERLEUKIN-10 GENE TRANSDUCTION 24???48 HOURS BEFORE DONATION1

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Abstract
Interleukin- (IL) 10 may be a potent regulator for controlling of allograft rejection.A single administration of IL-10 is not effective for controlling graft rejection. Gene transfer is an attractive vehicle for prolonging the expression of short-lived proteins. Donor or recipient livers were transduced with 1×1010 p.f.u. of replication-deficient adenovirus vectors harboring human IL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or after rat orthotopic liver transplantation. DA allografts given AdCMVhIL-10 24–48 hr before donation survived for more than 56 days in Lewis recipients, although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3 days after transplantation were rejected within 30 days in recipients. Serum levels of human IL-10 in gene-transferred rats were maximum from day 2 to 7. The serum level of human IL-10 then decreased gradually, and human IL-10 was not detected by ELISA 30 days after gene-transduction. In gene-transduced long-term surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was also up-regulated on posttransplant day 3, despite the expression of Th1 cytokines (IL-2 and interferon-γ), although in rejected liver allografts, IL-2 and interferon-γ were expressed without expression of IL-4 and IL-10. The prolongation of survival of IL-10 cDNA transferred liver allografts might be due to inhibition of the early phase of alloimmune-response by over expression of IL-10, despite the expression of IL-2 and interferon-γ.