title: Transcutaneous immunotherapy via laser-generated micropores efficiently alleviates allergic asthma in Phl p 5-sensitized mice.
abstract: BACKGROUND
  Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser-generated micropores to subcutaneous injection.
  
  
  METHODS
  BALB/c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen Phl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant-free Phl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; Phl p 5-specific serum levels of IgG1, IgG2a, and IgE; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed.
  
  
  RESULTS
  Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in Th2-associated cytokine secretion, transcutaneous application revealed a general downregulation of Th1/Th2/Th17 responses. Successful therapy was associated with induction of IgG2a and an increase in FOXP3+ CD4+ T cells.
  
  
  CONCLUSIONS
  Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy-associated boosting of systemic Th2 immunity. Immunotherapy via laser-microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy.
authors.affiliation: Division of Allergy and Immunology, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Bach
authors.forename: R
authors.initials: R
authors.lastname: Weiss
authors.forename: M
authors.initials: M
authors.lastname: Hessenberger
authors.forename: S
authors.initials: S
authors.lastname: Kitzmueller
authors.forename: E E
authors.initials: EE
authors.lastname: Weinberger
authors.forename: W D
authors.initials: WD
authors.lastname: Krautgartner
authors.forename: C
authors.initials: C
authors.lastname: Hauser-Kronberger
authors.forename: C
authors.initials: C
authors.lastname: Boehler
authors.forename: J
authors.initials: J
authors.lastname: Thalhamer
authors.forename: S
authors.initials: S
authors.lastname: Scheiblhofer
mesh_terms: D000279:Administration, Cutaneous; D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000628:therapy*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D007834:Lasers; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D007073:Immunoglobulin E; D010047:Ovalbumin