Effect of the H-1-receptor antagonist cetirizine on the stimulated expression of adhesion molecules and the activation of NF kappa B in human endothelial cells

Background in the present work, we studied the effect of cetirizine on the cytokine-stimulated immune response of human umbilical vein endothelial cel ls (HUVECs). Methods: Our research was directed to analyze the effect of pr eincubation of HUVECs with cetirizine (1 mug/ml) on (1)the INF alpha-, IL-4 - and IFN gamma -induced surface expression of ICAM-1 and VCAM-1, (2) the s ecretion of IL-6 and IL-8, (3) the recruitment of NF kappaB and AP-1 and (4 ) the adhesion of histiocytic monocytes (U937) to activated endothelial mon olayers. Results and Conclusion: Cetirizine exerts a stimulus-dependent pat tern of regulatory action on various parameters of endothelial cell activat ion. In detail, cetirizine significantly reduces the expression of ICAM-1 a nd VCAM-1 paralleled by a reduced monocytic adhesion in particular to TNF a lpha -activated HUVECs. With regard to the cytokine release, dual effects a re obtained by cetirizine: IL-6 and IL-8 secretion is suppressed by cetiriz ine in TNF alpha and IL-4-activated cells, whereas the IFN gamma -induced s uppression of IL-8 is nearly abrogated. In this context, the TNF alpha -ind uced signal transduction with regard to NF kappaB and AP-1 was also suppres sed by cetirizine. Copyright (C) 2001 S. Karger AG, Basel.