Mechanism of cyclosporin A-induced inhibition of prostacyclin synthesis by macrophages

Prostaglandins. 1985 Nov;30(5):735-47. doi: 10.1016/0090-6980(85)90004-8.


In vitro studies of PG production over a 24 h period by adherent rat peritoneal macrophages activated by serum-opsonized zymosan revealed that CSA (0.3-10 micrograms/ml) caused a dose-related inhibition of PGI2 (assayed as 6-oxo-PGF1 alpha) formation. Indomethacin (IND, 0.01-10 micrograms/ml) and dexamethasone (DEX, 0.01-10 micrograms/ml) also inhibited the PG production in a dose-related manner. When arachidonic acid (10 micrograms/ml) was added together with the inhibitors, there was no change in the level of PGI2 produced by IND-treated cells whilst the PGI2 levels of DEX- and CSA-treated cells were elevated to the control level. Therefore CSA like DEX does not inhibit cyclo-oxygenase activity. However unlike DEX, CSA (1-30 micrograms/ml) caused inhibition of phospholipase A2 (PLA2) activity when assayed on the hydrolysis of a synthetic substrate by pancreatic PLA2 in a cell-free system. The direct inhibition of PLA2 might well be a manifestation of the fundamental activity of CSA on immunocompetent cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / biosynthesis
  • Animals
  • Arachidonic Acid
  • Arachidonic Acids / metabolism
  • Cells, Cultured
  • Cyclosporins / pharmacology*
  • Depression, Chemical
  • Dexamethasone / pharmacology
  • Epoprostenol / biosynthesis*
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Macrophage Activation
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A2
  • Rats
  • Rats, Inbred Strains
  • Zymosan / pharmacology


  • Arachidonic Acids
  • Cyclosporins
  • Arachidonic Acid
  • 6-Ketoprostaglandin F1 alpha
  • Dexamethasone
  • Zymosan
  • Epoprostenol
  • Phospholipases A
  • Phospholipases A2
  • Indomethacin