Chemical structure and biological activity of endotoxins (lipopolysaccharides) and lipid A.

Lipopolysaccharides (endotoxins) of gram-negative bacteria consist of two components with distinct physico-chemical character: a heteropolysaccharide and a covalently linked lipid, termed lipid A. Chemically, lipid A is made up of acylated glucosamine disaccharides, which are interlinked by pyrophosphate bridges. Lipid A represents the toxic center of lipopolysaccharides. In rabbits, lipid A also induces pyrogen tolerance as well as pyrogen cross-tolerance. Fever tolerance can be passively transferred with serum from rabbits immunized with lipid A. The protective power of lipid A antiserum, however, is only expressed in amimals which have been pretreated with lipid A or lipopolysaccharide, indicating that other than humoral factors, perhaps cellular, also participate in endotoxin tolerance. Lipid A antiserum also prevents the local Shwartzman reaction in rabbits. The possible potency of lipid A antiserum to prevent other endotoxin effects such as lethal shock is presently investigated.