Contrasting effects of long-term treatment with IFN-γ in endothelial cells:: Increase in IL-6 secretion versus decrease in IL-8 secretion, NF-κB, and AP-1 activation

The benefit of neutrophil exclusion from type 1 T helper cell (TH1) inflammatory processes was demonstrated in clinical studies. Increased recruitment of lymphocytes and monocytes to endothelium and impaired recruitment of polymorphonuclear neutrophils (PMNs) following interferon-gamma (IFN-gamma) treatment were described. The present study demonstrates that a 24 h treatment with IFN-gamma increases interleukin (IL)-6 release but reduces IL-8 secretion of both untreated and of tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells (ECs), favoring the attraction of lymphocytes but not of neutrophils. Alteration of cytokine release was accompanied by reduced basal and TNF-alpha-stimulated nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) activity. However, IFN-gamma application neither altered gene expression of both TNF-alpha receptors (p55 and p75) nor cellular density of TNF-alpha receptor-2 (p75). Therefore, immune-modulatory action of IFN-gamma seems to be mediated by signal transduction molecules.