Pharmacological characterization of the leukocyte kinetics after intranasal antigen challenge in a guinea pig model of allergic rhinitis.
OBJECTIVE
We characterized the leukocyte kinetics after antigen challenge, and investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on this leukocyte response in a guinea pig model of allergic rhinitis.


METHODS
Male Hartley guinea pigs were used.


METHODS
Intranasally sensitized guinea pigs were challenged once every week for 15 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 15th challenge.


METHODS
The time-related changes in the numbers of differential leukocytes in nasal cavity lavage fluid (NCLF) and in peripheral blood after pollen inhalation challenge were investigated. The effects of the drugs on the antigen-induced changes in the leukocyte counts were evaluated. In addition, histopathological examination of the nasal mucosa was also performed 5 h after the challenge.


RESULTS
There was a marked increase in the number of leukocytes in NCLF, especially of eosinophils, which peaked at 5 h, after antigen challenge in this model. This response was also accompanied by the peripheral blood eosinophilia and neutrophilia. Seratrodast (30 mg/kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg) inhibited the eosinophilia in all of the blood, the nasal mucosa and NCLF seen 5 h after the antigen challenge. Terfenadine (10 mg/kg) had no apparent effect on the blood and the mucosal eosinophilia, although it tended to suppress the eosinophil accumulation in NCLF.


CONCLUSIONS
These results suggest that the present model is useful for analyzing the mechanisms of antigen-induced eosinophilic inflammation in allergic rhinitis and that both TXA2 and p-LTs, but not histamine, contribute to the antigen-induced eosinophilia in this model of allergic rhinitis.
Yamasaki
M L
ML
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan. Yamasaki_Masashi@takeda.co.jp
Sasaki
K
K
Mizutani
N
N
Nabe
T
T
Sakura
Y
Y
Matsumoto
T
T
Ashida
Y
Y
Kohno
S
S
D000281:Administration, Intranasal; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D016227:Benzoquinones / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology; D007700:Kinetics; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D020024:Leukotriene Antagonists; D008297:Male; D009296:Nasal Cavity / Q000473:pathology; D006255:Rhinitis, Allergic, Seasonal / Q000473:pathology*; D016593:Terfenadine / Q000494:pharmacology; D007507:Therapeutic Irrigation; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D000941:Antigens; D016227:Benzoquinones; D002867:Chromones; D006538:Heptanoic Acids; D020024:Leukotriene Antagonists; C060230:seratrodast; D013928:Thromboxane A2; D016593:Terfenadine; D003907:Dexamethasone; C047681:pranlukast