HISTAMINE INDUCES IL-6 PRODUCTION BY HUMAN ENDOTHELIAL-CELLS

Histamine is one of the major mediators implicated in the physiopathol ogy of allergy. On vascular endothelium, histamine mainly induces earl y effects: an increase in vasopermeability leading to oedema, a releas e of lipid mediators and a transient expression of P-selectin. The aim of this study was to evaluate the effects of histamine on adhesion mo lecule expression and IL-6 production by human endothelial cells. Hist amine did not modulate the expression of intercellular adhesion molecu le-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-select in, but induced a transient expression of P-selectin as previously rep orted. In addition, histamine increased in a dose- (from 10(-5) to 10( -3) M) and time- (from 4 h to 24 h) dependent fashion the IL-6 synthes is by endothelial cells. Tumour necrosis factor-alpha (TNF-alpha)-indu ced IL-6 production was also potentiated in a dose-dependent manner by histamine, without modification of the time course of IL-6 secretion. Moreover, this increase of IL-6 production induced by histamine was i nhibited in a dose-dependent manner by H1 and H2 histamine receptor an tagonists (50% inhibition of IL-6 production at 5 x 10(-4) M and 4 x 1 0(-5) M, respectively). So, histamine induces, besides already well kn own effects, a late stimulation of endothelial cells, i.e. the product ion of IL-6.