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.