Modulation of eosinophilic chemotaxis with azelastine and budesonide in allergic patients.
In this paper, the effect of azelastine hydrochloride, a potent inhibitor of leukotrienes (LTs) and H1 receptors for histamine, was assessed as regards modulation of in vitro eosinophilic chemotaxis. In this respect, chemotaxis of eosinophils (EOS), isolated from the peripheral blood of untreated allergic subjects in the acute phase, was significantly diminished after in vitro treatment with azelastine in comparison to values before treatment. When EOS were pre-incubated with serial dilutions of the drug, it was observed that azelastine inhibited chemotaxis in a dose-dependent fashion. Since azelastine acts in vitro as a regulator of the calcium pump, EOS were pre-incubated with different concentrations (0.6 and 3.0 mM) of Ca++. In these experimental conditions azelastine was able to reduce EOS chemotactic activity only in the presence of 0.6 mM Ca++, whereas with higher Ca++ concentrations (3.0 mM) the inhibitory effect of the drug was abrogated. On the other hand, particular attention was paid to inhaled budesonide, a non halogenated glucocorticosteroid derivative, structurally related to 16 alpha-hydroxy prednisolone, which represents a helpful for treatment mild to moderate asthma. Data obtained after in vitro treatment with budesonide of a group of allergic patients demonstrated that EOS chemotactic activity was significantly reduced in these subjects. Conclusively our data show that 1) azelastine acts as a dose-dependent antagonist of chemotaxis; 2) it may exert this action by inhibiting Ca++ flow into cells; 3) inhaled budesonide may induce inhibition of bronchial inflammation by downregulating EOS chemotactic capacity.
Ventura
M T
MT
Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Italy.
Giuliano
G
G
Di Corato
R
R
Tursi
A
A
D000293:Adolescent; D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008875:Middle Aged; D010793:Phthalazines / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D010793:Phthalazines; D019819:Budesonide; D000242:Cyclic AMP; D002118:Calcium; C020976:azelastine