Effects of a cysteinyl leukotriene antagonist, ONO-1078 (pranlukast), on total airway resistance after antigen challenge in sensitized guinea pigs

Objective and Design: To define the role of leukotriene (LT) in allergic rhinitis, we examined the effects of a cysteinyl (Cys) LT antagonist (ONO-1078, pranlukast).¶Material: Actively sensitized Dunkin-Hartley guinea pigs.¶Treatment: ONO-1078 (pranlukast), 3–100 mg/kg p.o. l h before antigen challenge.¶Methods: Nasal symptoms (sneezing, nasal scratches), changes of total airway resistance (TAR by plethysmography) and eosinophil infiltration into the nasal mucosa were determined following topical antigen (OA) challenge. Dunnet's test (TAR and symptoms) and the Mann-Whitney U-test (eosinophils) were applied.¶Results: Control animals showed bi-phasic nasal responses, peaking 10 min and 240 min after the topical antigen challenge, respectively. While the early-phase response was characterized by nasal symptoms of sneezing and scratching accompanied by the increase in TAR, the late-phase was characterized by an increase in TAR accompanied by eosinophil infiltration into nasal mucosa. The nasal symptoms (sneezing and scratching) were not inhibited by pretreatment with ONO-1078 at doses up to 100 mg/kg (p.o., n = 15). Although early peak responses of TAR were not affected with even the highest dose (30 mg/kg, p.o., n = 6), late-phase TAR peak response (control: 174.8 ± 8.2%, n = 6) were significantly inhibited by 10 mg/kg (142.7 ± 15.8%; p < 0.05, n = 6) and 30 mg/kg (118.0 ± 6.6%; p < 0.01, n = 6) of ONO-1078 (p.o.). In addition, the eosinophil infiltration induced by the antigen was not inhibited by ONO-1078 (30 and 100 mg/kg, p.o., n = 6).¶Conclusions: Our results suggest that Cys LT may play an important role in the late-phase increase in TAR in the guinea pig model of allergic rhinitis.