title: Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice.
abstract: BACKGROUND
  Several epidemiological and experimental studies have demonstrated that exposure to pathogens such as those from the genus Mycobacterium leads to the suppression of allergic sensitization and inflammation. However, little is known as to whether pathogen-derived soluble antigens have the potential to modulate the pathogenesis of allergic rhinitis.
  
  
  OBJECTIVE
  We sought to determine whether application of purified protein derivative (PPD) from Mycobacterium tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis using a recently developed murine model.
  
  
  METHODS
  First, we investigated whether a single intranasal application of PPD could elicit cytokine production in the nose by RT-PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni egg antigen (SEA) intranasally without an adjuvant. PPD was applied through different routes either before or after sensitization. The production of SEA-specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was compared among mice that had or had not received PPD treatment.
  
  
  RESULTS
  IFN-gamma, but not IL-4, was detected in the nasal tissue 12 to 48 h after a single intranasal application of 10 microg PPD. Repeated intranasal application of PPD prior to and during sensitization with SEA significantly inhibited the production of both SEA-specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially inhibited the production of IL-4 by nasal lymphocytes in response to SEA. Conversely, this treatment led to a significant increase in IFN-gamma production. On the other hand, PPD applied through the footpad had no effect over the same period. Repeated intranasal application of PPD after sensitization with SEA had no exacerbative effect on allergic inflammation.
  
  
  CONCLUSIONS
  These results indicate that the local application of PPD, and the subsequent induction of IFN-gamma, inhibits the initiation, but not the exacerbation, of allergic rhinitis in mice. This suggests that pathogen-derived antigens have potential for use in the prevention and prophylaxis of allergic rhinitis.
authors.affiliation: Department of Otolaryngology - Head & Neck Surgery,Okayama University Medical School, Okayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hattori
authors.forename: M
authors.initials: M
authors.lastname: Okano
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: A R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: D A
authors.initials: DA
authors.lastname: Harn
authors.forename: K
authors.initials: K
authors.lastname: Nishizaki
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D014373:Tuberculin / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D014373:Tuberculin; D007073:Immunoglobulin E