Effect of the H₁-Receptor Antagonist Cetirizine on the Stimulated Expression of Adhesion Molecules and the Activation of NFκB in Human Endothelial Cells

Abstract

Background: In the present work, we studied the effect of cetirizine on the cytokine-stimulated immune response of human umbilical vein endothelial cells (HUVECs). Methods: Our research was directed to analyze the effect of preincubation of HUVECs with cetirizine (1 µg/ml) on (1) the TNFα-, IL-4- and IFNγ-induced surface expression of ICAM-1 and VCAM-1, (2) the secretion of IL-6 and IL-8, (3) the recruitment of NFĸB and AP-1 and (4) the adhesion of histiocytic monocytes (U937) to activated endothelial monolayers. Results and Conclusion: Cetirizine exerts a stimulus-dependent pattern of regulatory action on various parameters of endothelial cell activation. In detail, cetirizine significantly reduces the expression of ICAM-1 and VCAM-1 paralleled by a reduced monocytic adhesion in particular to TNFα-activated HUVECs. With regard to the cytokine release, dual effects are obtained by cetirizine: IL-6 and IL-8 secretion is suppressed by cetirizine in TNFα and IL-4-activated cells, whereas the IFNγ-induced suppression of IL-8 is nearly abrogated. In this context, the TNFα-induced signal transduction with regard to NFĸB and AP-1 was also suppressed by cetirizine.

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