Implications of endotoxin contamination in the evaluation of antibodies to lipopolysaccharides in a murine model of gram-negative sepsis.
The pharmacological factors involved in lipopolysaccharide (LPS)-induced host resistance against infection were investigated in relation to the problem of endotoxin contamination of preparations of monoclonal antibody to the common structure of endotoxin. When administered prophylactically, purified LPS (as low as 4 ng/kg of mouse body weight) or antibody preparations contaminated with endotoxin (assayed by Limulus amoebocyte lysate test) were protective against lethal challenge with a clinical isolate of Escherichia coli (P less than .01). Antibodies that were nonreactive to LPS were similarly protective (P less than .001) when spiked with low doses of LPS (100 ng/mg of protein) but, as with LPS, were without effect when administered after infection. Endotoxin contamination of core-reactive antibody to LPS is mostly a problem associated with the large-scale production, purification, and concentration of the monoclonal antibody. The efficacy (as reported in studies in animal models of gram-negative bacterial sepsis) of antibody to LPS core is controversial. We suggest that endotoxin contamination is a likely factor in this controversy.
Chong
K T
KT
Department of Pharmacology, Cetus Corporation, Emeryville, California 94608.
Huston
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004340:Drug Contamination; D004731:Endotoxins / Q000276:immunology / Q000633:toxicity; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000628:therapy*; D007109:Immunity; D007136:Immunoglobulins / Q000276:immunology; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007136:Immunoglobulins; D008070:Lipopolysaccharides