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A biologically active substance produced by bacteria and consisting of lipopolysaccharide, a complex macromolecule containing a polysaccharide covalently linked to a unique lipid structure, termed lipid A. All gram-negative bacteria synthesize lipopolysaccharide, which is a major constituent of their outer cell membrane. One major function of lipopolysaccharide is to serve as a selectively permeable barrier for organic molecules in the external environment. Different types of gram-negative bacteria synthesize lipopolysaccharide with very different polysaccharide structures. The biological activity of endotoxic lipopolysaccharide resides almost entirely in the lipid A component. See Cell membranes, Lipid, Polysaccharide
When lipopolysaccharides are released from the outer membrane of the microorganism, significant host responses are initiated in humans and other mammals. It is generally accepted that lipopolysaccharides are among the most potent microbial products, known for their ability to induce pathophysiological changes, in particular fever and changes in circulating white blood cells. In humans as little as 4 nanograms of purified lipopolysaccharide per kilogram of body weight is sufficient to produce a rise in temperature of about 3.6°F (2°C) in several hours. This profound ability of the host to recognize endotoxin is thought to serve as an early warning system to signal the presence of gram-negative bacteria.
Unlike most microbial protein toxins (which have been termed bacterial exotoxins), endotoxin is unique in that its recognized mode of action does not result from direct damage to host cells and tissues. Rather, endotoxin stimulates cells of the immune system, particularly macrophages, and of the vascular system, primarily endothelial cells, to become activated and to synthesize and secrete a variety of effector molecules that cause an inflammatory response at the site of bacterial invasion. These mediator molecules promote the host response which results in elimination of the invading microbe. Thus, under these circumstances lipopolysaccharide is not a toxin at all, but serves an important function by helping to mobilize the host immune system to fight infection. See Cytokine, Immunology
Even though endotoxin stimulation of host cells is important to host defense against infection, overstimulation due to excess production of endotoxin can lead to serious consequences. Endotoxin-induced multiple-organ failure continues to be a major health problem, particularly in intensive care; it has been estimated that as many as 50,000 deaths annually occur in the United States as the result of endotoxin-induced shock.
Immunization of humans with endotoxin vaccines to protect against endotoxin shock has not been considered practical. Efforts to provide immunologic protection against endotoxin-related diseases have focused upon development of antibodies that recognize the conserved lipid A structure of endotoxin as a means of passive protection against the lethal effects of this microbial product. See Bacteria, Medical bacteriology, Vaccination