DOSE-RESPONSE EFFECT OF IN-VIVO ADMINISTRATION OF ENDOTOXIN ON POLYMORPHONUCLEAR LEUKOCYTES OXIDATIVE BURST

In vitro, endotoxin primes polymorphonuclear leukocytes (PMNs) to resp ond with a greater oxidative burst. The purpose of the present study w as to investigate the in vivo effect of a wide range of single endotox in bolus doses using a rat model. PMNs were subsequently challenged in vitro with phorbol ester to produce reactive oxygen intermediates (RO I). Flow cytometric determination of ROI production by PMNs using the dichlorofluorescin conversion assay showed that although low doses ind uced 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 st ill increasing after a low dose. Neutropenia occurred immediately afte r endotoxin injection. After 6 h, PMN counts returned to almost normal levels with a high dose, but rebound neutrophilia occurred with a sma ll dose. In contrast to in vitro studies, in vivo injection showed a r esponse pattern that varied widely with dose and time of observation.