Cytokine cascades and the hepatic inflammatory response to ischemia and reperfusion

Ischemia/reperfusion injury of the liver has two distinct phases that contribute to hepatocyte damage. The acute phase is characterized by Kupffer cell production of reactive oxygen species, which results in moderate hepatocyte injury. The later phase includes an intricate cascade of inflammatory events culminating in neutrophil infiltration of the postischemic liver. Accumulated neutrophils cause substantial injury to hepatocytes through their release of oxidants and proteases. This review discusses the mechanisms by which this inflammatory response is initiated, propagated, and regulated and the impact of these pathways on neutrophil-dependent injury to the liver.