Prostacyclin analogs suppress the synthesis of tumor necrosis factor-α in LPS-stimulated human peripheral blood mononuclear cells

doi:10.1016/0162-3109(93)90042-O

Immunopharmacology

Volume 26, Issue 3, November–December 1993, Pages 259-264

Immunopharmacology

https://doi.org/10.1016/0162-3109(93)90042-O Get rights and content

Abstract

Recent reports have shown that prostaglandin E₂ (PGE₂) is able to suppress lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α). In the present study we compared PGE₂ with prostacyclin (PGI₂) analogs in their potency to influence LPS-stimulated production of interleukin-1β (IL-1β) and TNF-α by human mononuclear cells (MNC). Our results show, that the stable analogs of PGI₂, iloprost and cicaprost, markedly suppress TNF-α synthesis in LPS-stimulated MNC without effect on IL-1β production. Although there was no significant difference in maximal suppression of TNF-α, iloprost and cicaprost reached suppression to 50% of control at 20-fold lower concentrations than PGE₂. The ID₅₀ for iloprost and cicaprost were 8 nM and 5 nM, respectively, compared to 125 nM for PGE₂. Moreover, the prostacyclin analogs as well as PGE₂ suppressed LPS-induced production of TNF-α in Mono Mac 6 cells, a permanent human cell line with characteristics of mature monocytes. Suppression of TNF-α synthesis by cicaprost and PGE₂ is probably mediated by an increased intracellular cAMP formation. We were able to show elevated cAMP levels with 1 μM and 10 μM of PGE₂ and cicaprost in this system. The suppression of TNF-α synthesis may add to the beneficial effects of iloprost reported in animal models of acute respiratory distress syndrom (ARDS) and may offer a therapeutic approach in TNF-α mediated pathologic processes.

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The ATIII therapy in inflammation is associated with a decrease in the interleukin (IL)-6 plasma levels and a down-regulation of plasma activity of intercellular adhesion molecule 1 and tumor necrosis factor (TNF) levels [30]. The therapeutic effect of ATIII on apoptosis may be the result of endothelial release of prostacyclin (PGI2), which inhibits the endotoxin-induced production of TNF-α [31]. Thus, the apoptosis rate may be an indirect target of the ATIII treatment (perhaps by decreasing TNF levels via endothelial release of PGI2), since we observed a change in apoptosis rates in the anastomotic region in the early healing period in the SIII group.
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Research paperProstacyclin analogs suppress the synthesis of tumor necrosis factor-α in LPS-stimulated human peripheral blood mononuclear cells

Abstract

Curr Opinion Gen. Dev.

Blood

Clin Immunol Immunopath

Prostaglandins

J Biol Chem

Int J Immunopharm

Biochem Biophys Res Commun

Cyclic nucleotides differentially regulate the synthesis of tumor necrosis factor-α and interleukin-1β by human mononuclear cells

Immunology

Interactive effects of the tumor necrosis factor promotor and 3′-untranslated regions

J Immunol

Prostacyclin in inflammation

Effects of prostaglandins and cAMP levels on monocyte IL-1 production

Agents Actions

Research paper
Prostacyclin analogs suppress the synthesis of tumor necrosis factor-α in LPS-stimulated human peripheral blood mononuclear cells