Hideki Ogasawara

Topical Antigen Provocation Increases the Number of Immunoreactive IL-4-, IL-5- and IL-6-Positive Cells in the Nasal Mucosa of Patients with Perennial Allergic Rhinitis

To evaluate the role of Th2-type cytokines in the nasal mucosa which has been repeatedly exposed to antigen, an immunohistological study for IL-4, IL-5 and IL-6 was performed in patients with perennial allergic rhinitis and non allergic rhinosinusitis. The numbers of immunoreactive (ir)-IL-4, ir-IL-5 and ir-IL-6-positive cells were significantly higher in allergic mucosa than in nonallergic mucosa. In allergic mucosa, the numbers of these ir-cytokine-positive cells were significantly higher in the antigen-challenged site than in the control site. When the patients were divided into an early group (4-6 h after challenge) and a later group (15-25 h after challenge), only the change of ir-IL-4-positive cells was remarkable in the former group, whereas those of the ir-IL-4, ir-IL-5 and ir-IL-6-positive cells were significant in the latter group. These results suggest that antigen-induced upregulation of IL-4, IL-5 and IL-6 is important in the pathogenesis of perennial allergic rhinitis.

Effects of Anti-IL-5 Monoclonal Antibody on the Murine Model of Nasal Allergy

IL-5 is known to be closely related to the infiltration, activation and proliferation of eosinophils. In this study, we evaluated the in vivo effects of anti-IL-5 monoclonal antibody (mAb) in the murine model of nasal allergy. The mAb treatment inhibited the antigen-induced late phase eosinophilia, but had no effects on the number of basophilic cells. It also inhibited early phase nasal symptoms, and tended to inhibit histamine hypersensitivity. These findings suggest that IL-5 plays an important role in the pathogenesis of allergic nasal disorders.

Role of CD4–Positive T Cells in the Pathogenesis of Nasal Allergy in the Murine Model

Background: Antigen–induced upregulation of cytokines, especially Th2–type cytokines, has been proven to be closely related to allergic inflammation in nasal allergy. CD4–positive T cells are supposed to play an important role not only in the induction of allergy but also in allergic inflammation. Methods: The anti–CD4 mAb was administered to the murine model of nasal allergy either at the beginning of sensitization, just before antigen challenge or during a topical booster sensitization. Then, the effects on the antigen–induced nasal responses and the serum level of antigen–specific IgE antibody were evaluated. Results: When the mAb was applied at the beginning of sensitization, the early–phase nasal symptoms and the late–phase nasal eosinophilia were significantly inhibited, and the 8–day passive cutaneous anaphylaxis (PCA) titer tended to be inhibited. When the mAb was applied just before the challenge, there were no differences in the nasal symptoms, the nasal eosinophilia or the 8–day PCA titer between the mAb–treated animals and the control animals. When the mAb was applied during a topical booster sensitization, the nasal eosinophilia, the 8–day PCA titer and histamine hypersensitivity were significantly suppressed in the treated animals. Conclusion: CD4–positive T cells play an important role in the induction of IgE–mediated nasal allergy, occurrence of late–phase allergic inflammation and histamine hypersensitivity, but not in antigen–induced early–phase nasal symptoms in the murine model. In cases of chronic topical antigen exposure, however, the suppressive effects of a single application of the anti–CD4 mAb are not remarkable.

Effects of cyclosporin A and glucocorticosteroids on antigen-induced hypersensitivity to histamine in a guinea pig model of allergic rhinitis

Abstract.Objective and Design: In an attempt to study the pathogenesis of mucosal hypersensitivity in allergic rhinitis, we investigated the suppressive effects of cyclosporin A (CyA) and glucocorticosteroids on ovalbumin (OA)-induced hypersensitivity to topical histamine challenge.¶Materials: Actively sensitized Dunkin-Hartley guinea pigs.¶Treatment: OA and alum were applied to guinea pigs intraperitoneally 3 times at two-week intervals. After general sensitization, OA inhalation was performed every day for 6 days as topical sensitization. Before inhalation, treatment with CyA (50 mg/kg, p.o.), glucocorticosteroids (beclomethasone propionate (1.0 mg/kg, i.p.), fluticasone propionate (FP, 0.5 mg/kg, i.p.)) or vehicle were performed, and the sensitivity to histamine was measured before and after the inhalation. Moreover, in actively (general and topical) sensitized guinea pigs, FP (0.5 mg/kg, i.p.) was applied every day for 5 days and histamine sensitivity was evaluated before and after the application.¶Results: We found that histamine sensitivity was significantly increased by nasal antigen challenge in this guinea pig model, and that the occurrence of histamine hypersensitivity was inhibited by the pretreatment with CyA and glucocorticosteroids. Although multiple administration of FP gradually reduced the histamine hypersensitivity according to the period of administration, it did not significantly alter the histamine hypersensitivity after the occurrence of hypersensitivity.¶Conclusion: It is concluded that CyA and glucocorticosteroids suppress antigen-induced histamine hypersensitivity in a guinea pig model of allergic rhinitis.

Effects of Emedastine on Guinea Pig Models of Allergic Rhinitis.

Emedastine difumarate is a selective H1-antagonist as well as a histamine release inhibitor. The effects of emedastine on patients with allergic rhinitis have been previously reported. We examined the effects of emedastine difumarate (0.03, 0.3 and 1.0mg/kg) on nasal symptoms, changes in the total airway resistance (TAR) and eosinophil infiltration into the nasal mucosa induced by topical antigen challenge in actively sensitized guinea pigs.Nasal symptoms (the number of sneezes and scratches) were significantly inhibited by emedastine pretreatment in a dose dependent manner. We noted a biphasic increase in the TAR after antigen challenge. The first peak response of the TAR was partially but significantly inhibited by emedastine (0.3 and 1.0mg/kg). The second peak response of the TAR was also inhibited by emedastine (1.0mg/kg). Furthermore, emedastine (1.0mg/kg) significantly inhibited antigen-induced eosinophil infiltration into the nasal mucosa.In conclusion, our results suggest that emedastine difumarate may suppress nasal symptoms in guinea pig models of allergic rhinitis.