CHANGES IN POLYMORPHONUCLEAR LEUKOCYTE SURFACE AND PLASMA BACTERICIDAL PERMEABILITY-INCREASING PROTEIN AND PLASMA LIPOPOLYSACCHARIDE-BINDING PROTEIN DURING ENDOTOXEMIA OR SEPSIS/

Objective: To evaluate changes in levels of polymorphonuclearleukocyte surface bactericidal/permeability-increasing protein (BPI), plasma BP I, and plasma lipopolysaccharide (LPS) binding protein (LBP) in normal human volunteers administered Escherichia coli LPS and in patients wi th sepsis and gram-negative infections. Design: Survey; case series. S etting: Clinical research center and surgical intensive care unit of a medical school and an associated tertiary care hospital. Patients or Other Partcipants: Volunteers (n=10) screened prior to study by histor y and physical examination to exclude those with underlying diseases o r hematologic abnormalities. Consecutive sample of surgical intensive care unit patients (n=10) meeting criteria for sepsis syndrome with gr am-negative infection. An additional patient with systemic inflammator y response syndrome but no gram-negative infection. All patients were studied on meeting the criteria. Three of the patients with sepsis syn drome and the patient with systemic inflammatory response syndrome wer e evaluated on recovery (approximately 25 days after initial study). B ecause these studies in volunteers and patients overlapped temporally, the control values were those of volunteers evaluated prior to LPS ad ministration. No matching was employed. Measurements and Results: Comp ared with controls, LPS-challenged volunteers and patients with sepsis bo th exhibited significant granulocytosis (P<.01) and increased conc entrations of polymorphonuclear leukocyte surface BPI (P<.01) and of p lasma LBP (P<.01). Plasma BPI concentrations were increased (P<.01) in volunteers following LPS administration. There was a trend toward inc reased concentrations of plasma BPI in patients, but this was not sign ificant relative to controls. Maximum concentrations of plasma LBP wer e approximately 250- and 3000-fold higher than plasma BPI concentratio ns in endotoxemic volunteers and in patients, respectively. Conclusion s: Circulating polymorphonuclear leukocytes increase expression of BPI in response to LPS or gram-negative sepsis. Subsequently, concentrati ons of plasma BPI and LBP increase. Because both LBP and BPI bind to L PS, it is suggested that endogenously derived plasma levels of BPI are likely to be inadequate to compete for LPS binding to the much more a bundant LBP in the circulation.