INHIBITORY EFFECTS OF INTERLEUKIN-6 ON RELEASE OF PGI(2) BY CULTURED HUMAN PULMONARY-ARTERY SMOOTH-MUSCLE CELLS

We evaluated the effect of interleukin-6 (IL-6) on the production of p rostacyclin (PGI(2)) 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 PGI9(2 ) in the culture medium. The incubation of HPASMC with 10 mu g/ml of l ipogolysaccharide (LPS), 200 U/ml of IL-1 beta, or 500 U/ml of TNF alp ha for 24 hr significantly increased the concentration of PGI(2) in th e medium. However, the addition of IL-6 to a medium containing LPS, IL -1 beta, or TNF alpha significantly inhibited the stimulatory effect o f those substances on PGI(2) production. Such inhibition was closely r elated to the concentration of IL-6. IL-6 may counteract the roles of LPS and of-other cytokines on the regulation of pulmonary vascular ten sion in endotoxin- and cytokine-mediated disorders such as sepsis and the acute respiratory distress syndrome (ARDS).