The effects of intravenous endotoxin on various host-effector molecules

To understand better the pathogenesis of gram-negative infections, we administered a single intravenous injection of Escherichia coli RE-2 endotoxin (4 ng/kg) to five normal volunteers and periodically measured various host-effector molecules in blood. All subjects had a significant (p less than 0.05) increase in temperature (maximum of 1.3 +/- 0.1 degrees C at 4 hours) and white blood cell count (maximum of 7700 +/- 1800 cells per cubic millimeters at 8 hours). Thymocyte costimulatory activity in blood was markedly increased 2 hours after endotoxin administration but returned to baseline at 4 hours. Blood cortisol and beta-endorphin levels paralleled each other, peaking 4 hours after endotoxin (mean increases of 21 +/- 14 micrograms/dl and p less than 0.01; 18.6 +/- 5.9 pg/ml and p less than 0.05, respectively) and returning to baseline at 8 hours. Blood histamine levels did not significantly change at any time point after endotoxin administration. Since thymocyte costimulatory activity was the first of the measured parameters to achieve peak blood levels, we suggest that endotoxin-induced increases in various cytokines may contribute to the increases in the other measured parameters and thereby play a significant role in the pathogenesis of gram-negative infections.