Secretion of IL-6, IL-8 and G-CSF by human endothelial cells in vitro in response to Staphylococcus aureus and staphylococcal exotoxins

The capacity of endothelial cells to produce and release cytokines (IL-6, I L-8 and C-CSF) in response to exposure to Staphylococcus aureus strains or staphylococcal exotoxins (alpha-toxin, enterotoxin A and TSST-1) was invest igated. An endothelial cell culture model of human umbilical vein endotheli al cells (HUVEC) was used. Five out of ten clinical isolates of S. aureus w ere found to induce cytokine production and release from endothelial cells. Four of the five isolates that induce cytokine release produced enterotoxi n A, B, C, D andor TSST-1, compared with two of those that did not induce r elease. Purified staphylococcal exotoxins (1 pg/ml - 1 mu g/ml) did not act as primary stimuli and induced no detectable cytokine secretion. When endo thelial cells were prestimulated with IL-1 beta or TNF alpha at a concentra tion of 1 ng/ml for 2 h, IL-1 beta served as a potent primary stimulus for IL-6, IL-8 and G-CSF production, whereas TNF alpha did not induce any signi ficant cytokine release during the subsequent 24 h. A further increase in I L-6 and G-CSF release, but not of IL-8, was observed when IL-1 beta prestim ulated cells were exposed to alpha-toxin or TSST-1. However, to potentiate cytokine production (IL-6 and IL-8) by SEA, both IL-1 beta and the toxin ha d to be present simultaneously. Our data show that S. aureus, but not staph ylococcal exotoxins, have the capacity to act as primary stimuli of endothe lial cells and induce production and release of cytokines. IL-1 beta may pr ime HUVEC to release IL-6, IL-8 and G-CSF prior to subsequent stimulation w ith staphylococcal exotoxins.