Characterization of a primate model of asthma using anti-allergy/anti-asthma agents.
The following study was performed to further characterize a primate model of asthma using classes of drugs that target allergy (pyrilamine, cetirizine), are bronchodilators for the treatment of asthma (salbutamol, salmeterol) or are anti-inflammatory (dexamethasone). These drugs were examined for their ability to inhibit acute, antigen-induced bronchoconstriction, the development of airway hyperresponsiveness (AHR) and the infiltration of leukocytes into the lungs of atopic cynomolgus monkeys (Macaca facsicularis) using a 10-day, multiple antigen (Ag) challenge protocol. All compounds except dexamethasone and cetirizine significantly (p < 0.05) reduced acute, Ag-induced bronchoconstriction (salbutamol: 74.2%, salmeterol: 52.6%%, pyrilamine: 62.4% inhibition) compared to vehicle control trials. Only dexamethasone and salmeterol prevented the development of AHR to methacholine challenge by 90.4 +/- 6.81% and 85.7 +/- 5.61% respectively. Dexamethasone significantly reduced the Ag-induced increase in BAL eosinophils by 85.9 +/- 8.53%. Cetirizine reduced the eosinophil response in 5 of 6 monkeys and salmeterol demonstrated a trend towards reduced eosinophil increases after multiple Ag challenge, but neither of these were statistically significant. These results further illustrate the utility of this model in predicting compound effects against several relevant functional endpoints that are consistent with the effects of similar classes of compounds in humans.
Turner
C R
CR
Department of Immunology and Infectious Diseases, Pfizer Central Research Groton, CT 06340, USA.
Andresen
C J
CJ
Smith
W B
WB
Watson
J W
JW
D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D017332:Cetirizine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D000068299:Salmeterol Xinafoate
D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D000941:Antigens; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D000068299:Salmeterol Xinafoate; D003907:Dexamethasone; D011738:Pyrilamine; D000420:Albuterol; D017332:Cetirizine