title: Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts.
abstract: BACKGROUND
  Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. 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.
  
  
  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) sublingual 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 histology was also investigated.
  
  
  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 sensitized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks.
  
  
  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.
authors.affiliation: Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Shima
authors.affiliation: Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: tkoya@med.niigata-u.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koya
authors.affiliation: Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tsukioka
authors.affiliation: Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Sakagami
authors.affiliation: Department of General Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Research Laboratory, Torii Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Fukano
authors.affiliation: Research Laboratory, Torii Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Katsuyo
authors.initials: K
authors.lastname: Ohashi-Doi
authors.affiliation: Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of General Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000737:chemistry*; D063729:Sublingual Immunotherapy / Q000379:methods*
chemical_list: D045424:Complex Mixtures
keywords: Airway hyperresponsiveness; Animal model; Bronchial asthma; House dust mites; Sublingual immunotherapy