Inhibitory effects of interleukin-6 on release of PGI2 by cultured human pulmonary artery smooth muscle cells.
We evaluated the effect of interleukin-6 (IL-6) on the production of prostacyclin (PGI2) by cultured human pulmonary artery smooth muscle cells (HPASMC). Incubation of these cells for up to 48 h with IL-6 led to a dose- and time-dependent decrease in the concentration of PGI2 in the culture medium. The incubation of HPASMC with 10 micrograms/ml of lipopolysaccharide (LPS), 200 U/ml of IL-1 beta, or 500 U/ml of TNF alpha for 24 hr significantly increased the concentration of PGI2 in the medium. However, the addition of IL-6 to a medium containing LPS, IL-1 beta, or TNF alpha significantly inhibited the stimulatory effect of those substances on PGI2 production. Such inhibition was closely related to the concentration of IL-6. IL-6 may counteract the roles of LPS and of other cytokines on the regulation of pulmonary vascular tension in endotoxin- and cytokine-mediated disorders such as sepsis and the acute respiratory distress syndrome (ARDS).
Wen
F Q
FQ
Second Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Watanabe
K
K
Yoshida
M
M
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D011464:Epoprostenol