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

Immunopharmacology. Nov-Dec 1993;26(3):259-64. doi: 10.1016/0162-3109(93)90042-o.

Abstract

Recent reports have shown that prostaglandin E2 (PGE2) is able to suppress lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-alpha (TNF-alpha). In the present study we compared PGE2 with prostacyclin (PGI2) analogs in their potency to influence LPS-stimulated production of interleukin-1 beta (IL-1 beta) and TNF-alpha by human mononuclear cells (MNC). Our results show, that the stable analogs of PGI2, iloprost and cicaprost, markedly suppress TNF-alpha synthesis in LPS-stimulated MNC without effect on IL-1 beta production. Although there was no significant difference in maximal suppression of TNF-alpha, 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-alpha in Mono Mac 6 cells, a permanent human cell line with characteristics of mature monocytes. Suppression of TNF-alpha synthesis by cicaprost and PGE2 is probably mediated by an increased intracellular cAMP formation. We were able to show elevated cAMP levels with 1 microM and 10 microM of PGE2 and cicaprost in this system. The suppression of TNF-alpha synthesis may add to the beneficial effects of iloprost reported in animal models of acute respiratory distress syndrome (ARDS) and may offer a therapeutic approach in TNF-alpha mediated pathologic processes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Dinoprostone / pharmacology
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology
  • Humans
  • Iloprost / pharmacology*
  • Interleukin-1 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Prostaglandins, Synthetic / pharmacology*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Interleukin-1
  • Lipopolysaccharides
  • Prostaglandins, Synthetic
  • Tumor Necrosis Factor-alpha
  • Epoprostenol
  • Iloprost
  • Dinoprostone
  • cicaprost