Inhibition of Endotoxin-Induced Macrophage Tumor Necrosis Factor Expression by a Prostacyclin Analogue and Its Beneficial Effect in Experimental Lipopolysaccharide Intoxication

Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)-stimulated macrophages. It could be demonstrated by bioassays that LPS-induced TNF production was suppressed in a dose-dependent manner when macrophages were treated with iloprost at the time of LPS stimulation. Northern blot analysis revealed that iloprost inhibited TNF production at the transcription level. In vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be significantly (P less than .05) reduced by iloprost administration. It is assumed that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in septic shock.