Are Events After Endotoxemia Related to Circulating Phospholipase A2 ?

Abstract

Objective The authors sought to determine whether the signs and symptoms of endotoxemia were related to the endotoxin–stimulated increase in circulating phospholipase A₂ (PLA₂) activity. Background Because hypotension and pulmonary injury have been associated with elevated PLA₂ activity in septic shock and PLA₂ levels are reduced with the administration of glucocorticoids, the PLA₂ response to endotoxin was investigated in volunteers pretreated with and without hydrocortisone. Methods Carefully screened human subjects were studied under four conditions: (1) saline, (2) hydrocortisone, (3) endotoxin, and (4) hydrocortisone administration before endotoxin exposure. Pulse rate, blood pressure, temperature, and symptoms of endotoxemia were serially measured. Plasma for tumor necrosis factor concentrations and PLA₂ activity was obtained. Results After lipopolysaccharide, pulse rate and tumor necrosis factor concentrations rose at 1 to 2 hours; temperature increased maximally at 4 hours. PLA₂ activity reached peak levels at 24 hours. With hydrocortisone pretreatment, a 50% reduction in the concentrations of tumor necrosis factor and PIAa occurred. Significant correlations between other variables and PLA₂ activity were not observed. The enzyme identified by monoclonal antibody was the secreted nonpancreatic PLA₂ (SNP-PLA₂). Conclusions The results of this study suggest that elevations in circulating SNP-PLA₂ activity and systemic events associated with intravenous endotoxin administration are unrelated.