DISTINCT FUNCTIONAL ACTIVITIES IN CANINE SEPTIC SHOCK OF MONOCLONAL-ANTIBODIES SPECIFIC FOR THE O-POLYSACCHARIDE AND CORE REGIONS OF ESCHERICHIA-COLI LIPOPOLYSACCHARIDE

Monoclonal antibodies (MAbs) specific for O polysaccharide or core oli gosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (L PS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intrap eritoneal implantation of an E. coli O111:B4-infected clot. Animals we re further randomized to ceftriaxone or saline. O-specific MAb signifi cantly reduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial press ure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone, sur vival was enhanced by O-specific MAb (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 receiving O-specific MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08 vs. controls). These data support the co mplex role of LPS in sepsis and the discrete functional effects of MAb s specific for different elements of LPS.