RELATIVE CONCENTRATIONS OF ENDOTOXIN-BINDING PROTEINS IN BODY-FLUIDS DURING INFECTION

Endotoxin initiates the systemic inflammatory response, haemodynamic c hanges, and multi-organ failure that may occur as a consequence of sys temic gram-negative bacterial infection. The serum protein lipopolysac charide-binding protein (LBP) binds to the lipid A component of bacter ial endotoxin and facilitates its delivery to the CD14 antigen on the macrophage, where proinflammatory cytokines are released and a cascade of host mediators is initiated. The neutrophil granular protein bacte ricidal/permeability-increasing protein (BPI) competes with LBP for en dotoxin binding and functions as a molecular antagonist of LBP-endotox in interactions. We have measured concentrations of both proteins in b ody fluids from 49 consecutive patients. In 16 of 17 samples of fluid from closed-space infections, BPI was present in greater concentration than LBP (median BPI/LBP ratio 7.6 [95% CI 2.32-22.1]), The ratio of BPI and LBP was not significantly different from 1.0 in abdominal flui d from 10 patients with peritonitis (ratio 0.235 [0.18-0.47]), whereas the BPI/LBP ratio was low in 22 non-infected body fluids (0.01 [0.001 -0.04]) and concentrations of both proteins approached those in normal human plasma. BPI concentrations were directly correlated with the qu antity of neutrophils within clinical samples (r(s) = 0.81, p < 0.0001 ). Thus, within abscess cavities BPI is available in sufficient quanti ties for effective competition with LBP for endotoxin. BPI may attenua te the local inflammatory response and the systemic toxicity of endoto xin release during gram-negative infections.