Inhibitory effect of cetirizine on cytokine-enhanced in vitro eosinophil survival.
BACKGROUND
Cetirizine is an antihistamine that inhibits in vivo eosinophil influx into the inflamed airways following allergen challenge, and in vitro eosinophil chemotaxis and adhesion. Since eosinophils are proposed to have an important role in the pathophysiology of asthma and allergic disease, the effects of cetirizine on eosinophil function may be a mechanism of this agent's therapeutic regulation of the allergic reaction.


OBJECTIVE
To determine the effect of cetirizine on in vitro eosinophil survival.


METHODS
Using human eosinophils isolated from patients with allergic rhinitis, the cells were cultured in vitro for 48 to 72 hours with medium, cetirizine, or dexamethasone in the presence of IL-5, IL-3, or GM-CSF. Eosinophil survival was assessed by trypan blue exclusion.


RESULTS
In the presence of IL-5, but not GM-CSF or IL-3 100 microM cetirizine significantly inhibited eosinophil survival at 48 and 72 hours; the magnitude of this inhibition was dependent on cytokine concentration. Although cetirizine significantly suppressed cytokine promotion of eosinophil survival, it was not as potent as dexamethasone.


CONCLUSIONS
Although the in vitro concentration of cetirizine was required to be quite high, cetirizine may affect in vivo airway inflammation through its inhibition of IL-5-dependent eosinophil survival.
Sedgwick
J B
JB
Department of Medicine, University of Wisconsin, Madison, USA.
Busse
W W
WW
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017332:Cetirizine / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D006801:Humans; D007377:Interleukin-3 / Q000037:antagonists & inhibitors; D015848:Interleukin-5 / Q000276:immunology; D008875:Middle Aged; D012130:Respiratory Hypersensitivity / Q000097:blood; D012220:Rhinitis / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017332:Cetirizine