LEUKOTRIENE B-4 PRODUCTION BY BLOOD NEUTROPHILS IN ALLERGIC RHINITIS - EFFECTS OF CETIRIZINE

Background Mucosal inflammatory processes in late phase of allergic di seases involve cytokine production, cell adhesion molecule overexpress ion and release of inflammatory mediators with chemotactic activity, s uch as leukotriene B-4 (LTB(4)). We had previously observed increased production of LTB(4) by neutrophils in patients with allergic rhinitis and discussed the role of granulocyte macrophage-colony stimulating f actor (GM-CSF) priming. Some antihistaminic compounds were shown to di minish the production of leukotrienes by neutrophils. Objective In a f irst step, we evaluated in ex vivo and in vitro studies, the effects o f cetirizine on LTB(4) production by blood neutrophils from allergic a nd healthy subjects. In a second step, we studied the in vitro effect of cetirizine on LTB(4) production by neutrophils from healthy subject s during GM-CSF priming of these cells. Methods Neutrophils from both populations were purified from venous blood and LTB(4) production was measured using high performance liquid cromatography (HPLC) method. Re sults In ex vivo studies, cetirizine treatment induced a decreased LTB (4) production by neutrophils in allergic rhinitis. This effect of dec reased LTB(4) production was reproduced in vitro with 10(-8)-10(-6) M cetirizine. Nevertheless, this anti-H1 compound had no effect on neutr ophil priming with GM-CSF. Conclusion As LTB(4) is an important chemot actic factor, Cetirizine could act on inflammatory cell recruitment by inhibiting LTB(4) production by neutrophils.