Levocetirizine and cytokine production and apoptosis of human eosinophils.
Antihistamines are a common therapy for allergic symptoms. Eosinophilic infiltration is considered a hallmark of allergic inflammation. Eosinophils are capable of mediating airway mucosal damage by producing various inflammatory mediators including cytokines, chemokines, basic granule proteins, lipid mediators, and growth factors. Reduced eosinophil apoptosis is thought to be an important feature in the formation of eosinophilia in allergic diseases such as allergic rhinitis, atopic eczema, and asthma. The aim of this study was to investigate the effects of levocetirizine on the production of inflammatory mediators by eosinophils and on eosinophil apoptosis. The production of cytokines and other inflammatory mediators by human eosinophils was measured by a cytokine antibody array. Apoptosis of isolated human eosinophils was assessed by measuring the relative DNA content of propidium iodide-stained cells. Of the 40 cytokines studied, levocetirizine (1 microM) was found to enhance the release of tissue inhibitor of metalloproteinases 1 and 4, matrix metalloproteinase 9, and heparin-binding epidermal growth factor and to attenuate the production of interleukins (IL)-1 beta and IL-7 and stem cell factor in lipopolysaccharide-stimulated human eosinophils. Levocetirizine did not alter constitutive eosinophil apoptosis or eosinophil survival induced by IL-5, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, or salbutamol. The results of this study suggest that levocetirizine modulates the profile of inflammatory mediators including cytokines, growth factors, proteinases, and antiproteinases produced by eosinophils, which may be of importance in allergic inflammation and airway remodeling. However, eosinophil longevity seems not to be modulated by levocetirizine.
The Immunopharmacology Research Group, Medical School, University of Tampere, Tampere, Finland.
Hannele
H
Hasala
Mirkka
M
Janka-Junttila
Eeva
E
Moilanen
Hannu
H
Kankaanranta
D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017332:Cetirizine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*
D016207:Cytokines; D039563:Histamine H1 Antagonists, Non-Sedating; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010879:Piperazines; C472067:levocetirizine; D017332:Cetirizine