Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts

  • Shima Kenjiro
    Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences
  • Koya Toshiyuki
    Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences
  • Tsukioka Keisuke
    Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences
  • Sakagami Takuro
    Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences
  • Hasegawa Takashi
    Department of General Medicine, Niigata University Medical and Dental Hospital
  • Fukano Chiharu
    Research Laboratory, Torii Pharmaceutical Co., Ltd.
  • Ohashi-Doi Katsuyo
    Research Laboratory, Torii Pharmaceutical Co., Ltd.
  • Watanabe Satoshi
    Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences
  • Suzuki Eiichi
    Department of General Medicine, Niigata University Medical and Dental Hospital
  • Kikuchi Toshiaki
    Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences

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<p>Background: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immu-notherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts.</p><p>Methods: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or high-dose (5 mg/day) sub-lingual HDM extracts for 2 weeks, followed by an additional week of intranasal exposure. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, cytokine levels in the BALF and lymph node cell culture supernatants, and allergen-specific antibodies were measured. Lung his-tology was also investigated.</p><p>Results: In mice sensitized for 5 weeks, high-dose SLIT ameliorated AHR, airway eosinophilia and goblet cell metaplasia. In mice sensitized for 3 weeks, even low dose SLIT ameliorated AHR and airway eosinophilia. Th2 cytokine levels in culture supernatants of submandibular lymph node cells in high-dose SLIT mice decreased, whereas IL-10 levels increased. Total IgA in BALF increased in mice sensi-tized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks.</p><p>Conclusions: These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation.</p>

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