Effect of a novel anti-allergic agent, HSR-609, on antigen-induced airway hyperresponsiveness in mice.
The effects of a newly synthesized anti-allergic agent, HSR-609, on allergic airway hyperresponsiveness and airway inflammation have been studied in sensitized mice. The effects were compared with those of two histamine H(1) receptor antagonists, cetirizine and terfenadine, and prednisolone. Three inhalations of antigen caused an increase in leukocytes (including eosinophils) with increases in IL-5 in BALF and airway hyperresponsiveness to acetylcholine in BALB/c mice. All drugs were orally administered once a day for 10 days from the day before the first inhalation of antigen. HSR-609 (10 mg/kg) and prednisolone (5 mg/kg) significantly inhibited the antigen-induced airway hyperresponsiveness, whereas cetirizine (10 mg/kg) or terfenadine (100 mg/kg) did not affect this airway response. At the same time HSR-609 inhibited the antigen-induced eosinophilia and IL-5 production in BALF. Prednisolone also showed an inhibitory effect on the airway eosinophilia and IL-5 production but not cetirizine and terfenadine in the same experiments. In addition, HSR-609 (p.o.) dose-dependently suppressed the accumulation of eosinophils elicited by antigen-stimulated D10G4.1 cells, a murine Th2 clone, in peritoneal cavity lavage fluid in AKR/J mice. These results suggest that HSR-609 inhibits allergic airway hyperresponsiveness to acetylcholine probably because of the inhibition of Th2-dependent eosinophilia caused by IL-5. In addition, effects of HSR-609 were different from those of cetirizine and terfenadine concerning the inhibition of antigen-induced airway hyperresponsiveness in mice.
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
K
K
Musoh
Y
Y
Maeda
H
H
Tanaka
N
N
Inagaki
H
H
Nagai
D000109:Acetylcholine; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001584:Benzoxepins / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D017332:Cetirizine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000473:pathology; D011239:Prednisolone / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*; D016593:Terfenadine / Q000627:therapeutic use
D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D001584:Benzoxepins; C104838:HSR 609; D006634:Histamine H1 Antagonists; D011725:Pyridines; D016593:Terfenadine; D011239:Prednisolone; D000109:Acetylcholine; D017332:Cetirizine