Leukotriene B4 production by blood neutrophils in allergic rhinitis--effects of cetirizine.
BACKGROUND
Mucosal inflammatory processes in late phase of allergic diseases involve cytokine production, cell adhesion molecule overexpression and release of inflammatory mediators with chemotactic activity, such as leukotriene B4 (LTB4). We had previously observed increased production of LTB4 by neutrophils in patients with allergic rhinitis and discussed the role of granulocyte macrophage-colony stimulating factor (GM-CSF) priming. Some antihistaminic compounds were shown to diminish the production of leukotrienes by neutrophils.


OBJECTIVE
In a first step, we evaluated in ex vivo and in vitro studies, the effects of cetirizine on LTB4 production by blood neutrophils from allergic and healthy subjects. In a second step, we studied the in vitro effect of cetirizine on LTB4 production by neutrophils from healthy subjects during GM-CSF priming of these cells.


METHODS
Neutrophils from both populations were purified from venous blood and LTB4 production was measured using high performance liquid cromatography (HPLC) method.


RESULTS
In ex vivo studies, cetirizine treatment induced a decreased LTB4 production by neutrophils in allergic rhinitis. This effect of decreased LTB4 production was reproduced in vitro with 10(-8)-10(-6)M cetirizine. Nevertheless, this anti-H1 compound had no effect on neutrophil priming with GM-CSF.


CONCLUSIONS
As LTB4 is an important chemotactic factor, Cetirizine could act on inflammatory cell recruitment by inhibiting LTB4 production by neutrophils.
Cheria-Sammari
S
S
Centre Hospitalier Lyon-Sud, Laboratoire D'Immuno-allergologie, Unité INSERM U352, Pierre-Benite, France.
Aloui
R
R
Gormand
F
F
Chabannes
B
B
Gallet
H
H
Grosclaude
M
M
Melac
M
M
Rihoux
J P
JP
Perrin-Fayolle
M
M
Lagarde
M
M
D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism; D017332:Cetirizine / Q000494:pharmacology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000378:metabolism*
D018926:Anti-Allergic Agents; D006634:Histamine H1 Antagonists; D007975:Leukotriene B4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017332:Cetirizine