Distinct Functional Activities in Canine Septic Shock of Monoclonal Antibodies Specific for the O Polysaccharide and Core Regions of Escherichia coli Lipopolysaccharide

Abstract

Monoclonal antibodies (MAbs) specific for O polysaccharide or core oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an E. coliO111 :B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantlyreduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial pressure from day 4 to 28 (P = .02). In dogs not receivingceftriaxone, survival was enhanced by O-specificMAb (4/5) compared with core-specific MAb (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but survival was prolonged in antibiotic-treated animals also receivingO-specific MAb(P = .02 vs. core-specific MAband controls) or core-specific MAb(P = .08 vs. controls). These data support the complex role ofLPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS.