Dose-response effect of in vivo administration of endotoxin on polymorphonuclear leukocytes oxidative burst

In vitro, endotoxin primes polymorphonuclear leukocytes (PMNs) to respond with a greater oxidative burst. The purpose of the present study was to investigate the in vivo effect of a wide range of single endotoxin bolus doses using a rat model. PMNs were subsequently challenged in vitro with phorbol ester to produce reactive oxygen intermediates (ROI). Flow cytometric determination of ROI production by PMNs using the dichlorofluorescin conversion assay showed that although low doses induced priming, large doses induced a decrease in ROI production by the few PMNs that remained in the circulation. By 6 h after injection, ROI production had returned to basal levels after a high dose, and was still increasing after a low dose. Neutropenia occurred immediately after endotoxin injection. After 6 h, PMN counts returned to almost normal levels with a high dose, but rebound neutrophilia occurred with a small dose. In contrast to in vitro studies, in vivo injection showed a response pattern that varied widely with dose and time of observation.