Prolongation of cardiac allograft survival with intracoronary viral interleukin-10 gene transfer

Abstract

EX VIVO gene transfer has the potential to deliver biologically active molecules to either the graft itself or defined sites in the recipient, leading to the expression of molecules capable of inhibiting immune response, resulting in local modulation of immunity after grafting. The replication-deficient adenovirus (Adv) has increasingly been used as a vehicle for gene delivery due to its high level of transfectability to target cells, regardless of the cell cycle, and also due to its high viral titers. Recent studies have shown that IL-10 inhibits monocyte production of IL-12, an important cytokine for Th1 cell differentiation and cellmediated immunity. Viral IL-10 (vIL-10), a product encoded by Epstein–Barr virus, is structurally homologous to murine and human IL-10, and shares many of their biological properties. In this study, we evaluated the use of adenoviral vector encoding vIL-10 in a major histoincompatible rat heterotopic cardiac transplant model to examine the effect of transfected vIL-10 in prolongation of allograft survival.