PAF and TNFα Interactions in the Pathophysiology of Septic Shock

Abstract

The septic shock syndrome is a medical emergency caused in part by the release into the circulation of bacterial lipopolysaccharide (LPS) endotoxin. The evolving concept in the pathophysiology of septic shock suggests that endotoxin induces its detrimental effects indirectly through the production of multiple mediators among which platelet activating factor (PAF) and tumor necrosis factor-a (TNFa) play a major role. The role of PAF and TNFa in endotoxemia was inferred from the following observations: 1 ) many of the manifestations of septic shock such as hypotension, hemoconcentration, thrombocytopenia and leukopenia can be produced by PAF and TNFa (Table 1 ); 2) elevated levels of PAF and TNFa were found in various septic conditions (Table 2); and 3) PAF antagonists and anti-TNFa neutralizing antibodies were shown to convey significant protection in animal models of septic shock (Table 3).