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 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. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantly reduced 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 receiving ceftriaxone, survival 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 complex role of LPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS.
Hoffman
W D
WD
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
Pollack
M
M
Banks
S M
SM
Koev
L A
LA
Solomon
M A
MA
Danner
R L
RL
Koles
N
N
Guelde
G
G
Yatsiv
I
I
Mouginis
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology; D001831:Body Temperature; D001835:Body Weight; D002443:Ceftriaxone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology* / Q000302:isolation & purification; D006439:Hemodynamics; D008070:Lipopolysaccharides / Q000276:immunology*; D019081:O Antigens; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008070:Lipopolysaccharides; D019081:O Antigens; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D002443:Ceftriaxone