Prednisolone inhibits cytokine-induced adhesive and cytotoxic interactionsbetween endothelial cells and neutrophils in vitro

We assessed whether prednisolone influenced the ability of human polymorpho nuclear neutrophils (PMN) to adhere to and cause lysis of human umbilical v ein endothelial cells (HUVEC) in vitro (as measured by the release of Cr-51 ). Pretreatment of the endothelium with IL-1 beta or tumour necrosis factor -alpha (TNF-alpha) caused prominent endothelial E-selectin expression and e ndothelial hyperadhesiveness for neutrophils, as well as PMN-mediated cytot oxicity. All these processes were dose-dependently reduced when prednisolon e was added to the assay system. This protective effect remained when HUVEC alone were pretreated with the drug prior to washing and cytokine activati on. Likewise, when HUVEC cytotoxicity was induced by the nitric oxide (NO) donor S-nitroso-acetyl-penicillamine (SNAP), prednisolone reduced cell inju ry significantly. In contrast, prednisolone did not interfere with signalli ng systems between TNF-alpha-stimulated HUVEC and quiescent PMN such as IL- 8 generation and release of cytosolic Ca2+ in the PMN. Thus, in this in vit ro model of vasculitis, prednisolone dose-dependently reduced cytokine-indu ced E-selectin expression and HUVEC hyperadhesiveness for neutrophils, as w ell as reducing neutrophil-dependent cytotoxicity against HUVEC via NO-depe ndent steps.