Evaluation of Non-Steady-State Neutrophil Kinetics During Endotoxin-Induced Granulocytosis

The mechanism by which bacterial endotoxin induces granulocytosis in man has been investigated by labeling granulocytes with radioactive diisopropylfluorophosphate. In man, a moderate dose of bacterial endotoxin produces a granulocytosis. By labeling circulating granulocytes with DF³²P and later giving endotoxin intravenously, the rates of granulocyte inflow and egress from the blood were measured. Equations were written which express these flow rates as a function of the variables derived from the experimental data. These equations were solved for several time intervals during the 24-hr experiments in each of 12 normal subjects. In the six subjects in whom there was a significant granulocytic response to endotoxin there was a mean increase of 180% (58-383) in the rate of granulocyte inflow to the blood and 150% (24-420) in the rate of egress of granulocytes from the blood during the 5-hour period immediately after endotoxin injection. The remaining six subjects did not have a granulocyte response beyond the 99% limits of normal and there was random variation of inflow and egress of granulocytes. In vitro studies with DFP-labeled cells incubated with endotoxin failed to demonstrate a direct effect of endotoxin on the cell label.