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

Objective: To define whether endothelin-1, a peptide produced by injur ed/ischemic endothelium, has any effect on monocyte intracellular calc ium and the production of interleukin (IL)-1 and IL-6. Design: Prospec tive controlled laboratory study. Human monocytes from healthy donors were assayed for intracellular calcium by fluorometry and were stimula ted for 24 hrs in tissue culture with purified endotoxin or endothelin . Setting: Veterans Affairs Medical Center surgical critical care basi c science laboratory. Measurements and Main Results: Endothelin-1 incr eased the intracellular calcium concentration in fura-2 loaded human m onocytes to a mean value of 37 +/- 4 nmol. Phytohemagglutinin increase d 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 e ndothelin significantly increased IL-6 production to values nearly as high as the Lipopolysaccharide controls, but did not increase IL-1 pro duction (n = 8; p < .01). Conclusion: Endothelin-1 increased intracell ular calcium in monocytes and caused production of IL-6.