Effects of C5a and FMLP on interleukin-8 production and proliferation of human umbilical vein endothelial cells

Interleukin-8 (IL-8), C5a and N-formyl-methionyl-leucyl-phenylalanine (fMLP ) are chemotactic peptides with predominant effects on leukocytes during in flammation. With emphasis on C5a we studied the regulation of the productio n of IL-8 by human umbilical vein endothelial cells (HUVEC) in vitro. Prima ry HUVEC cultures were incubated with IL-1 alpha, TNF alpha, C5a and fMLP f or 24 h and 48 h prior to measurement of IL-8 in supernatants of the cells by an enzyme immunoassay. Whereas IL-1 alpha and TNF alpha significantly in creased the levels of IL-8, C5a decreased the IL-8 production after 48 h. L n addition, the ability of IL-1 alpha, TNF alpha, C5a, fMLP and IL-8 to ind uce cell proliferation was compared by means of a H-3-thymidine incorporati on assay. In contrast with IL-1 alpha and TNF alpha, both C5a and fMLP incr eased cell proliferation of HUVEC. This increase occurred with increasing c oncentrations of C5a contrary to IL-8, which showed increased eel prolifera tion at low, but not high IL-8 concentrations.