Allograft transduction of IL-10 prolongs survival following orthotopic liver transplantation

Abstract

Interleukin-10 (IL-10) is an ideal candidate cytokine for AdCMVhIL-10 induced a prolongation of median survival suppressing the alloimmune response in transplantation.to more than 87 days, with two of five transduced grafts To determine whether genetic modulation of the hepatic showing more than 100 days of ongoing survival, when graft with IL-10 could prolong survival following orthotopic compared with 11 days for grafts transduced with a control liver transplantation, we constructed a replication-deficient adenovirus vector carrying the E. coli ␤-galactosidase adenovirus vector expressing human IL-10 (AdCMVhILgene (P = 0.0021) and 11 days for untreated grafts 10). Intraportal injection of this vector into a donor rat 24-(P = 0.0021). Pathological findings occurring in the 48 h before grafting resulted in efficient release of IL-10AdCMVhIL-10-transduced hepatic grafts revealed no eviinto the circulation of a recipient rat after transplantation.dence of progressive rejection reaction resulting in graft Moreover, levels of hIL-10 from the suprahepatic venafailure. These results demonstrate that hepatic grafts cava were significantly (1.48-fold) higher than those from modulated by IL-10 gene transfer make local and effective the infrahepatic vena cava (P = 0.013), indicating local ILimmunosuppression feasible in the transplantation setting. 10 production within the transduced hepatic graft.

A Vaccinia Virus Armed with Interleukin-10 Is a Promising Therapeutic Agent for Treatment of Murine Pancreatic Cancer

“…The long-held paradigm of IL10 function suggests it as an immunosuppressive cytokine, commonly investigated therapeutically in the context of treatment for inflammatory autoimmune conditions and allograft survival (41,42). However, using these two different murine models of pancreatic cancer, we observed significantly enhanced therapeutic responses after treatment with our IL10-armed vaccinia virus compared with unarmed virus.…”

Perspectives for Gene Therapy in Renal Diseases

“…IL-4 gene overexpression prolonged the renal survival (84). In contrast, there is no report to show that IL-10 gene therapy prolongs the survival of the renal allograft, although cardiac and liver allografts are reported to be improved the survival (85,86).…”

Gene therapy in transplantation in the year 2000: moving towards clinical applications?

“…Cellular IL-10 has also been reported to promote permanent liver graft acceptance 17 and prolong cardiac allograft survival in rats. 18 In both cases, local rejection mechanisms were inhibited, although generalized systemic immunosuppression was not assessed.…”