The importance of anti‐lipid A (anti‐endotoxin): Prevention of “shock lung” and acute renal failure

Abstract

Gram‐negative septicemia or endotoxinemia frequently causes a Shwartzman reaction that results in acute renal failure. Susceptibility to the lipid‐A, which has a common chemical structure in all gram‐negative bacteria, is ascribable to the fact that anti‐lipid A (antitoxin) titers are low in normal persons. This is because exposure is minimal since endotoxins cannot normally cross the bowel mucosa. Even during bacteremia, lipid‐A is a concealed antigen on the surface of bacteria, but it can be liberated by bactericidal antibiotics or by the action of complement in bacteremic shock. The consequences of endotoxinemia are so disastrous that there is a case for active or passive immunization to lipid‐A. Anti‐lipid A is vital as the antitoxin and has great protective potential, but it is nevertheless not the opsonin for phagocytosis of whole bacteria. Thus, antibodies to the innumerable O‐ and R‐antigens of lipopolysaccharides also play a part in resistance to gram‐negative septicemia.

Murine monoclonal antibodies to Klebsiella pneumoniae protect against lethal endotoxemia and experimental infection with capsulated K. pneumoniae

“…The incidence of gram-negative bacteremias is increasing, and shock occurs in about 40% of cases, with 40 to 90% mortality (24,33). Many difficulties remain in the treatment of these bacteremias, since gram-negative bacteria are often resistant to antibiotics and, furthermore, since this pathology occurs frequently in patients who are weakened by other underlying diseases.…”

“…No cross-reactivity is observed with these antibodies. In contrast, it has been postulated that antibodies directed against less well-exposed but more highly conserved elements of the core and lipid A regions of LPS possess cross-reactive and protective properties (5, 9, 33,35). Antibodies directed against these masked, highly conserved antigenic determinants may be obtained either by immunization with rough mutants, which lack the 0 antigen and thus partially reveal the core-lipid A regions (1,6,20,36), or by inoculation of LPS-associated proteins plus LPS (LAP-LPS) (12).…”