The role of leukotriene D₄ in septic shock models

Septic shock is a major complication during the treatment of intense care patients. A similar pathologic state can be experimentally induced in rodents by application of endotoxins. There is circumstantial as well as direct evidence for a participation of leukotriene D4 in this experimental multiorgan failure. Due to liver-specific sensitivation by galactosamine endotoxin-induced multiorgan failure can be experimentally transposed to a single organ, i.e. hepatic failure. Data presented here show a participation of the eicosanoid leukotriene D₄ in either model of sepsis. We have recently described a cellular system modelling endotoxin-induced hepatic failure. In this system based on the coculture of hepatocytes and nonparenchymal liver cells leukotriene D₄ is required for the development of cytotoxicity. It is concluded that the three models share pivotal mechanistic principles and might be used complementary to each other in order to study underlying molecular events.