Suppressive activity of epinastine hydrochloride on eosinophil activation in vitro.
The influence of a histamine H1 receptor antagonist, epinastine hydrochloride (EP), on eosinophil functions was examined in vitro and in vivo. The first set of experiments was undertaken to examine whether EP could suppress eosinophilia and IgE hyperproduction induced by Mesocestoides cortii infection in BALB/c mice. The number of peripheral blood eosinophils and levels of IgE were examined 21 days after infection. Oral administration of EP at a daily dose of 0.3 mg/kg, which is the recommended human therapeutic dose, for 21 days was not able to suppress either peripheral blood eosinophilia or IgE hyperproduction, which was observed in mice infected with M. cortii. The second part of the experiment was designed to examine the influence of EP on eosinophil activation induced by stem cell factor (SCF) stimulation in vitro. Eosinophils were obtained from M. cortii-infected mice and stimulated with SCF in the presence of different concentrations of EP for 24 h. The addition of EP into cell cultures suppressed eosinophil activation induced by SCF stimulation as assessed by measuring the contents of acronym for Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES), macrophage inflammatory protein-1beta (MIP-1beta) and leukotriene C4 (LTC4) levels in culture supernatants. The minimum concentration of EP which caused significant suppression of factor productions was 25 ng/ml, which is similar to the concentration in plasma after oral administration of the therapeutic dose in humans. These results may suggest that EP exerts inhibitory effects on eosinophil activation and results in favorable modification of the clinical status of allergic patients.
Mochizuki
Yu-ichiro
Y
Department of Otolaryngology, School of Medicine, Showa University, Tokyo, Japan.
Furuta
Atsuko
A
Furuya
Ayako
A
Kanai
Ken-ichi
K
Asano
Kazuhito
K
Suzaki
Harumi
H
D000818:Animals; D002478:Cells, Cultured; D002590:Cestode Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004802:Eosinophilia / Q000097:blood; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D008645:Mesocestoides / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D019089:Stem Cell Factor / Q000494:pharmacology
C503460:Ccl5 protein, mouse; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D003984:Dibenzazepines; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D019089:Stem Cell Factor; D017997:Leukotriene C4; D007073:Immunoglobulin E; C053090:epinastine