Intranasal Challenge of Cynomolgus Monkeys with Ascaris,Ragweed,Bradykinin,and Histamine

Seven feral monkeys with Ascaris hypersensitivity confirmed by intradermal skin test were challenged with single doses of Ascaris extract (10⁵ PNU/nostril), ragweed extract (10³ PNU/nostril) and diluent; with increasing doses of bradykinin (0.1, 1, and 5 mg/nostril) and histamine (0.1, 1, and 5 mg/nostril), and with repeated doses of PBS diluent. Total mean nasal resistance (TMNR) was measured by rhinomanometry and eustachian tube function by the forced-response test. For single dose challenges, testing was conducted before and 5, 15, 40, and 50 minutes after the challenge and for multiple dose challenges before, 5 and 15 minutes after each dose, and 40 and 50 minutes after the final dose. Mean TMNR (cm H₂O/L/sec) was increased from 28.9 ± 9 at baseline to peak at 124 ± 46 after Ascaris challenge. In contrast, TMNR was unaffected in six of seven monkeys challenged with diluent and in all monkeys challenged with ragweed. Progressive TMNR increases from baseline (25 ± 8) were observed for bradykinin (peak = 64 ± 46) and histamine (peak 108.4 ± 59) challenges. Eustachian tube function data showed no significant changes after intranasal provocation with either allergens or mediators. Provocative intranasal allergen challenge in actively sensitized monkeys is an effective method for evaluating the pathophysiology of allergic rhinitis and the effect of inflammatory mediators on nasal resistance.