Human cytokines modulate arterial vascular tone via endothelial receptors

Only a few cytokines have been tested for their possible role in modulating vascular function. Moreover, no direct effect of cytokines on vascular tone has yet been thoroughly studied. We therefore examined whether a wide range of well-defined cytokines could directly affect vascular tone in isolated human arterial and venous segments from various organs. We found that the cytokines stem cell factor (maximal response with 1 mM), granulocyte colony-stimulating factor (0, 1 mM) and erythropoietin (1 mM) relaxed, while tumor necrosis factor alpha (0.1 mM), interleukin (IL) 6 (10 mM) and IL-10 (0.1 mM) induced contraction of arterial but not of venous segments. The cytokines (maximal concentration tested was 1 mM) IL-3, IL-5, IL-13, macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor had no apparent effects on either arterial or venous tone. These vascular effects were endothelium-dependent as denuded arteries did not respond to any cytokine, and inhibition of nitric oxide synthase or endothelin receptor A abrogated the cytokine-induced changes in vascular tone. With immunohistochemistry we found receptors for the active cytokines on the arterial endothelium. In conclusion, several cytokines may modulate arterial vascular tone via endothelium-dependent mechanisms. Therefore cytokines might significantly modify blood supply to inflamed or ischemic tissues with elevated local concentrations of cytokines.