Lipoxygenase inhibitors suppress formation of tumor necrosis factor in vitro and in vivo.
The LPS induced synthesis of tumor necrosis factor in macrophage cultures, as determined in a fibroblast cytolysis assay was found to be effectively blocked by inhibitors of lipoxygenases. Likewise, the presence of tumor necrosis factor in serum of D-galactosamine sensitized mice after challenge with endotoxin was suppressed by the lipoxygenase inhibitors. Indomethacin, a blocker of cycclooxygenase was neither in vivo nor in vitro effective in the prevention of the endotoxin-induced synthesis of TNF. From LPS-treated macrophages we were able to isolate 13-hydroxylinoleic acid, a lipoxygenase product, which is significantly increased after LPS treatment of the cells, covalently bound to cellular constituents and may, therefore, be possibly involved in the formation of TNF.
Schade
U F
UF
Forschungsinstitut Borstel, FRG.
Burmeister
I
I
Engel
R
R
Reinke
M
M
Wolter
D T
DT
D000818:Animals; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D008041:Linoleic Acids / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008041:Linoleic Acids; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C042835:13-hydroxylinoleic acid; D005688:Galactosamine