['Ischemia-reperfusion (I/R) injury is a prime inflammatory factor in the dysfunction of orthotopic liver transplants. Interleukin (IL)-13 suppresses macrophage production of proinflammatory mediators. This study explores the effects of adenovirus (Ad)-based IL-13 gene transfer in rat models of hepatic I/R injury.', 'The authors used a model of warm in situ ischemia followed by reperfusion, and ex vivo cold ischemia followed by transplantation.', 'In a model of warm in situ ischemia followed by reperfusion, Ad-based IL-13 significantly diminished hepatocellular injury, assessed by serum glutamic oxaloacetic transaminase (SGOT) levels, as compared with Ad-based beta-galactosidase (gal)-treated livers. In a model of ex vivo cold ischemia followed by transplantation, the survival of liver grafts increased from 50% in Ad-beta-gal untreated controls to 100% after Ad-IL-13 gene therapy. This beneficial effect correlated with improved liver function (SGOT levels), preservation of hepatic histologic integrity and architecture (Suzuki criteria), and depression of neutrophil infiltration (myeloperoxidase assay). Ad-IL-13 diminished activation of macrophage-neutrophil-associated tumor necrosis factor-alpha, macrophage inflammatory protein-2, and endothelial-dependent E-selectin, but increased type 2 IL-4 and IL-13 expression.'] Does interleukin-13 gene transfer protect rat livers from antigen-independent injury induced by ischemia and reperfusion?