Anti-endotoxin therapeutic options for the treatment of sepsis.
The identification of lipopolysaccharide binding protein (LBP) and CD14 as key molecules in the cellular response to endotoxin has been a major advance in unravelling the pathophysiological basis of Gram-negative sepsis. Much interest has focused on developing effective anti-endotoxin treatments to abrogate the inflammatory consequences of Gram-negative infection. The therapeutic options can be divided into those aimed at neutralizing or clearing circulating endotoxin, including anti-endotoxin antibodies and endotoxin neutralizing proteins, and those that antagonize the effects of endotoxin on human cells--for example, lipid A analogues. Initial experiences with anti-lipopolysaccharide antibodies have been disappointing but a new generation of anti-endotoxin agents is about to enter clinical trials. Whether these will prove sufficiently effective to reduce the morbidity and mortality of Gram-negative sepsis remains to be seen.
Lynn
W A
WA
Cameron Centre, Ealing Hospital, Southall, Middlesex, UK.
D004727:Endothelium / Q000276:immunology; D004731:Endotoxins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007136:Immunoglobulins; D007167:Immunotherapy; D008050:Lipid A / Q000031:analogs & derivatives; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D015398:Signal Transduction
D004731:Endotoxins; D007136:Immunoglobulins; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; C042866:antilipopolysaccharide antibodies