ENDOTOXIN-INDUCED CHANGES OF ENDOTHELIAL-CELL VIABILITY AND PERMEABILITY - PROTECTIVE EFFECT OF A 21-AMINOSTEROID

Endotoxic shock results in endothelial cell dysfunction and oedema for mation. Endotoxin decreased in a concentration-dependent fashion endot helial cell viability with maximum effects by adding 10 mu g/ml lipopo lysaccharide for 48 h (47 +/- 15% and 22 +/- 2.6% of control cells in the presence or absence of foetal calf serum, respectively). Furthermo re, incubation (10 h) with lower concentrations of lipopolysaccharide (1 mu g/ml) significantly increased endothelial cell permeability to 2 50% compared to control values. The 21-aminosteroid U-74389G (10 mu M) prevented the cytotoxic effect of lipopolysaccharide as well as the l ipopolysaccharide-induced increase in endothelial cell permeability. B y contrast, the glucocorticoid methylprednisolone was less effective e ven at higher concentrations (100 mu M). The effect of lipopolysacchar ide is possibly due to oxidative stress and/or membrane destabilizatio n rather than to the induction of inflammatory mediators, because of t he reduced efficacy of the glucocorticoid.