[Effects of anti-PAF agents on nasal response after allergen challenge in guinea pigs]

We previously reported that Platelet-activating factor (PAF) activities were detected in nasal lavage fluids from patients with allergic rhinitis and in ovalbumin (OA) sensitized guinea pigs after topical allergen challenge. In guinea pigs, a topical application of PAF produced an increase in nasal vascular permeability which was inhibited by a PAF-antagonist (CV3988). To define the role of PAF in allergic rhinitis, we examined the effects of anti-PAF agents (WEB2086) and anti-allergic agents (Azelastine) on nasal airway resistance (NAR) and nasal symptoms in actively sensitized guinea pigs. Guinea pigs (200-300g) were sensitized by intraperitoneal injection of OA (10 micrograms/kg) and alum (5mg/kg) three times at two week intervals and repeated inhalation of OA (1mg/min., for 3 minutes) everyday for four weeks. The NAR was measured serially for 6 hours by an apparatus using the oscillation method. NAR change was expressed as a percent ratio to the pre-challenge value. Nasal symptoms were evaluated by counting the number of sneezing discharges and scratching movements for 30 minutes. The anti-PAF agent or Azelastine were administered orally at 2-3 hours before the topical allergen challenge. We noted a biphasic increase in NAR after allergen challenge. The increase in NAR during early phase was not affected but that during late phase was significantly inhibited by the anti-PAF agent and Azelastine. The nasal symptoms were inhibited by WEB2086 and Azelastine. Our results suggest that PAF activities might play an important role in late phase NAR increase following allergen challenge.