Arachidonic acid stimulates interleukin-6 release from rat peritoneal macrophages in vitro: evidence for a prostacyclin-dependent mechanism.
Interleukin-6 (IL-6) is a cytokine involved in the differentiation of B-cells to antibody secreting plasma cells, the activation of T-cells, and the stimulation of hepatocyte production of acute phase proteins. Because of the pro-inflammatory effects of this cytokine, we investigated the ability of the fatty acid arachidonic acid (AA) to regulate the release of IL-6 from rat resident peritoneal macrophages (M phi) in vitro. AA (0.5-16 microM) stimulated IL-6 release during a 4 h incubation period in a biphasic manner, with 4 microM AA generating a peak of IL-6 release (3-5-fold). AA (0.5-16 microM) also induced an increasing release of the AA metabolite thromboxane B2 (TXB2). The AA-induced release of IL-6 occurred within 1-2 h of incubation, whereas TXB2 concentrations were elevated within 5 min of AA treatment. The TX synthetase inhibitor CGS 12970 (4.0 microM and 40.0 microM) effectively blocked the generation of TXB2, but increased prostacyclin (PGI2) generation and potentiated the release of IL-6. In addition, PGI2, as well as the PGI2 agonists iloprost and cicaprost, stimulated IL-6 release from M phi by greater than 5-fold over vehicle-treated basal levels. These data suggest that PGI2 (but not TXA2) is involved in AA-induced IL-6 release from peritoneal M phi.
Holladay
C S
CS
Department of Physiology, Medical University of South Carolina, Charleston 29425-2258.
Wright
R M
RM
Spangelo
B L
BL
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D015850:Interleukin-6; D011465:Prostaglandins, Synthetic; D011725:Pyridines; D016718:Arachidonic Acid; D013928:Thromboxane A2; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D016285:Iloprost; C043867:cicaprost