Lipoxygenase inhibitors but not site specific 5-lipoxygenase blockers protect against endotoxic shock and inhibit production of tumor necrosis factor.
In the present study it was found that lipoxygenase inhibitors prevent LPS-, but not tumor necrosis factor alpha (TNF alpha)-evoked lethality. The specific 5-lipoxygenase inhibitors (MK-886, CGS-8515) were uneffective in endotoxin-induced shock. The 5-lipoxygenase inhibitors interfered with LTC4 formation in macrophages while they did not affect endotoxin induced TNF alpha-formation, neither in cell cultures nor in mice. The potency of other, less specific lipoxygenase blockers to suppress TNF alpha formation correlated quantitatively with their ability to interfere with 13-HODD synthesis. Based on the fact that a tight correlation exists between inhibition of TNF alpha synthesis and 13-HODD formation, this product might be important for TNF alpha formation.
Schade
F U
FU
Forschungsinstitut Borstel, FRG.
Engel
R
R
Jakobs
D
D
D000818:Animals; D002460:Cell Line; D008041:Linoleic Acids / Q000096:biosynthesis; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D013189:SRS-A / Q000096:biosynthesis; D012772:Shock, Septic / Q000139:chemically induced / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008041:Linoleic Acids; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D014409:Tumor Necrosis Factor-alpha; C024348:13-hydroxy-9,11-octadecadienoic acid