Agonists and antagonists for lipopolysaccharide-induced cytokines.
Agonistic and antagonistic properties of LPS and partial structures in the induction of cytokines are reviewed. Studies on structure-activity relationships of LPS and lipid A with human mononuclear cells reveal that S- and notably R-form LPS are very potent cytokine inducers. Synthetic E. coli lipid A is somewhat less active, whereas synthetic S. minnesota-type lipid A is significantly less active. Pentaacylated forms of lipid A are less potent than hexaacylated forms, and tetraacylated synthetic precursor Ia and bisacylated disaccharides and monosaccharides are completely inactive, indicating that a structure-dependent hierarchy of LPS and lipid A partial structures determines the monokine-inducing capacity in human mononuclear cells. Precursor Ia is a potent LPS antagonist. The mechanism of its inhibitory activity is shown to be due to competitive binding to cellular binding sites (receptors). Proinflammatory and antiinflammatory cytokines, receptor antagonists, and soluble cytokine receptors influence the cytokine-inducing activity of LPS, suggesting a complex regulatory network.
Flad
H D
HD
Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, Germany.
Loppnow
H
H
Rietschel
E T
ET
Ulmer
A J
AJ
D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004926:Escherichia coli; D006017:Glycolipids / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008050:Lipid A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D012486:Salmonella typhimurium; D013329:Structure-Activity Relationship
D016207:Cytokines; D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; C040142:lipid A precursors, bacterial; C044283:lipid X