Dopamine attenuates the chemoattractant effect of interleukin-8: A novel role in the systemic inflammatory response syndrome

Activated neutrophil (PMN) adherence to vascular endothelium comprises a ke y step for both transendothelial migration and initiation of potentially de leterious release of PMN products. The biogenic amine, dopamine (DA), has b een used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion rece ptor expression and on the endothelial molecules, E-selectin and ICAM-1, wa s evaluated. PMN were isolated from healthy controls, stimulated with lipop olysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treate d with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were ass essed flow cytometrically. In a separate experiment, the chemoattractant pe ptide, IL-8, was placed in the lower chamber of transwells, and PMN migrati on was assessed. Human umbilical vein endothelial cells (HUVEC) were stimul ated with LPS/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There wa s a significant increase in transendothelial migration in stimulated PMN co mpared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b/CD18 was significantly upregulated in stimulated PMN compared with normal PMN ( 252.4/352.4 vs. 76.7/139.4, P < 0.001) as were endothelial E-selectin/ICAM- 1 expression compared with normal EC (8.1/9 vs. 3.9/3.8, P < 0.05). After t reatment with dopamine, PMN transmigration was significantly decreased comp ared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine als o attenuated PMN CD11b/CD18 and the endothelial molecules E-selectin and IC AM-1 compared with stimulated PMN/EC that were not treated dopamine (174/24 0 vs. 252/352, P < 0.05 and 4/4.4 vs. 8.1/9, P < 0.05. respectively). The c hemoattractant effect of IL-8 was also attenuated. These results identify f or the first time that dopamine attenuates the initial interaction between PMN and the endothelium, and consequently, modulates PMN exudation. Thus, b iogenic amines, including dopamine, may function as anti-inflammatory cytok ines.