INTERLEUKIN-1 POTENTIATES HISTAMINE-INDUCED RELEASE OF PROSTACYCLIN FROM HUMAN ENDOTHELIAL-CELLS

1. In human cultured umbilical vein endothelial cells, interleukin-1 potentiated histamine-induced release of prostacyclin in a time- and concentration-dependent manner. 2. In cells incubated with interleukin-1 for 24 h, maximal potentiation was observed when cells were pre-incubated with 0.5 u ml-1 interleukin-1 before stimulation with histamine (1 μM - 1 mM). 3. In cells incubated with 0.5 u ml-1 interleukin-1, 20 min pre-incubation was sufficient to induce a statistically significant potentiation of prostacyclin release induced by 1 μM histamine (P < 0.05). 4. Nifedipine but not cycloheximide, significantly (P < 0.05) inhibited histamine-induced release of prostacyclin and interleukin-1 potentiation of histamine-induced release of prostacyclin (P < 0.05). 5. Incubation with 1 u ml-1 interleukin-1 induced a two fold increase in cellular prostaglandin synthetase activity within 30 min. The enzyme activity increased up to 6 h and was maintained up to 24 h. In cells co-incubated with cycloheximide and 1 u ml-1 interleukin 1, prostaglandin synthetase activity at 24 h was the same as that in unstimulated cells. Prostacyclin release was not significantly inhibited in cells co-incubated with cycloheximide and interleukin 1. 6. These results suggest that interleukin-1 potentiates histamine-induced release of prostacyclin by rapid up-regulation of prostaglandin synthetase activity as well as by inducing synthesis of enzyme protein. These mechanisms may act to potentiate/regulate vascular endothelial responses in inflammatory reactions.