ARE EVENTS AFTER ENDOTOXEMIA RELATED TO CIRCULATING PHOSPHOLIPASE A(2)

Objective The authors sought to determine whether the signs and symptoms of endotoxemia were related to the endotoxin-stimulated increase in circulating phospholipase A(2) (PLA(2)) activity. Background Because hypotension and pulmonary injury have been associated with elevated PLA, activity in septic shock and PLA(2) levels are reduced with the administration of glucocorticoids, the PLA(2) 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 PLA(2) 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. PLA, activity reached peak levels at 24 hours. With hydrocortisone pretreatment, a 50% reduction in the concentrations-of tumor necrosis factor and PLA(2) occurred. Significant correlations between other variables and PLA(2) activity were not observed. The enzyme identified by monoclonal antibody was the secreted nonpancreatic PLA, (SNP-PLA(2)). Conclusions The results of this study suggest that elevations in circulating SNP-PLA(2) activity and systemic events associated with intravenous endotoxin administration are unrelated.