ENDOTHELIN-1 INCREASES INTRACELLULAR CALCIUM IN HUMAN MONOCYTES AND CAUSES PRODUCTION OF INTERLEUKIN-6

Objective: To define whether endothelin-1, a peptide produced by injured/ischemic endothelium, has any effect on monocyte intracellular calcium and the production of interleukin (IL)-1 and IL-6. Design: Prospective controlled laboratory study. Human monocytes from healthy donors were assayed for intracellular calcium by fluorometry and were stimulated for 24 hrs in tissue culture with purified endotoxin or endothelin. Setting: Veterans Affairs Medical Center surgical critical care basic science laboratory. Measurements and Main Results: Endothelin-1 increased the intracellular calcium concentration in fura-2 loaded human monocytes to a mean value of 37 +/- 4 nmol. Phytohemagglutinin increased intracellular calcium in control monocytes to a mean value of 97 +/- 12 nmol (n = 15; p < .001). Endothelin had no effect on neutrophil or lymphocyte intracellular calcium. Monocytes incubated with 10(-9) M endothelin significantly increased IL-6 production to values nearly as high as the Lipopolysaccharide controls, but did not increase IL-1 production (n = 8; p < .01). Conclusion: Endothelin-1 increased intracellular calcium in monocytes and caused production of IL-6.