Effects of anti-lipid A human monoclonal antibody on lipopolysaccharide-induced toxicity to the kidney.
Studies were done to evaluate the effects of the human monoclonal anti-lipid A IgM antibody A6(H4C5) on several components of the hemodynamic and renal toxicity of the cell wall lipopolysaccharide of E. coli 0111:B4. Antibody (0.25 to four mg./kg. BW) was administered 0.5 hour before, or premixed for one hour with, lipopolysaccharide (0.05 mg./kg., a 14 to 18% lethal dose), and the following measurements made over 0.5 to 3.5 hours of study: systemic arterial blood pressure, renal plasma flow, and glomerular filtration. The proximal tubular cell cytotoxicity of 90 mg./kg. of the cephalosporin cephaloridine was also quantified in similarly treated animals sacrificed 48 hours later. While one mg./kg. of antibody prevented the reduction by the lipopolysaccharide of renal plasma flow, it did not prevent the nephrotoxic synergy with cephaloridine, and four times the antibody dose did not prevent lipopolysaccharide-induced hypotension or reduced glomerular filtration. These amounts of this antibody protect leukopenic rabbits against the lethality of the slow onset bacteremic model of Pseudomonas conjunctivitis. It is suggested that the incompleteness of protection in this study may be the result of the sensitivity of the assay methods used and/or the acute endotoxemia produced in these animals.
Tune
B M
BM
Department of Pediatrics, Stanford University School of Medicine, California 94305.
Hsu
C Y
CY
Bieber
M M
MM
Teng
N N
NN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001794:Blood Pressure; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000628:therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D007674:Kidney Diseases / Q000628:therapy*; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D011817:Rabbits; D012079:Renal Circulation
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides