Chronic endotoxemia reversibly alters respiratory burst activity of circulating neutrophils

Endotoxin-induced sequestration of neutrophils and ectopic activation of the cytocidal respiratory burst are thought to contribute to the pathophysiology of "endotoxin shock." The effects of endotoxin on the circulating neutrophil population have not been described. A rat model of continuous sublethal endotoxin infusion by minipump was used to study spontaneous and stimulus-specific activation and priming of superoxide anion and chemiluminescence production of circulating neutrophils. At 3 hr of endotoxin infusion there are marked neutropenia, minimal spontaneous activation compared to an active response in the control, and no priming effect. By 30 hr of endotoxin infusion, a neutrophilic leukocytosis, a marked spontaneous activation of superoxide anion and chemiluminescence production are observed, with no priming response and a loss of zymosan-stimulated chemiluminescence. The biologic significance of endotoxin-induced spontaneous activation is unknown. By 78 hr of infusion the host tolerance to endotoxemia is also evident for neutrophils, since neutrophil responses are nearly identical in endotoxin- and saline-infused groups. The loss of zymosan-stimulated chemiluminescence in both groups at 78 hr suggests a foreign-body effect from the minipump and may reflect altered arachidonic acid metabolism.