CORTICOSTEROIDS INDUCE PROLIFERATION BUT DO NOT INFLUENCE TNF- OR IL-1-BETA-INDUCED ICAM-1 EXPRESSION OF HUMAN DERMAL MICROVASCULAR ENDOTHELIAL-CELLS IN-VITRO

The effects of hydrocortisone, dexamethasone, betamethasone 17-valerat e and clobetasol propionate at concentrations of 10(-5)-10(-12) M on t he proliferation of human dermal microvascular endothelial cells (HDME C) were studied in vitro. In addition, confluent HDMEC were treated wi th TNF (1000 U/ml) or IL-1beta (1000 U/ml) alone or in combination wit h the corticosteroids (10(-5) M, 10(-6) M) for 24 h, and cytokine-indu ced expression of intercellular adhesion molecule-I (ICAM-1) was asses sed by immunocytochemistry. Controls were treated either with growth m edium or with the corticosteroids alone. All tested corticosteroids st imulated HDMEC growth after 4 and 6 days of treatment in a dose-depend ent manner, as assessed by H-3-thymidine incorporation and the 4-methy lumbelliferyl heptanoate (MUH) assay. The minimal effective concentrat ion was 10(-9) M for hydrocortisone, 10(-10) M for dexamethasone and b etamethasone, and 10(-12) M for clobetasol. In untreated and in cortic osteroid-treated cultures, less than 5% of the cells expressed ICAM-1. TNF and IL-1beta were strong inducers of ICAM-1 expression on 74% and 82% of the cells, respectively. None of the tested corticosteroids si gnificantly influenced cytokine-induced ICAM-1 expression, suggesting that the anti-inflammatory effects of corticosteroids are not related to ICAM-1 modulation on HDMEC.