Correlation of antibiotic-induced endotoxin release and cytokine production in Escherichia coli - Inoculated mouse whole blood ex vivo

Abstract

Escherichia coli were incubated in mouse whole blood ex vivo supplemented with β-lactam antibiotics that possessed preferential affinities for penicillin-binding proteins (PBPs). After 4 h, viable bacteria were undetectable in the presence of any of the 3 antibiotics tested, whereas significant increases in colony-forming units were detected in samples not treated with antibiotics. Differential levels of endotoxin in platelet-rich plasma were detected using the limulus amebocyte lysate assay, according to differential antibiotic affinities for the various PBPs. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in antibiotic-treated cultures after 8 h of incubation correlated well with the levels of endotoxin at 4 h (r = .96, P < .0001 for TNF-α; r = .91, P = .0002 for IL-6). These data indicate that differential affinities of β-lactam antibiotics for PBPs affect both endotoxin and cytokine responses ex vivo in mouse blood and correlate with in vivo protective efficacy of these antibiotics in gram- negative experimental models.