Airway inflammation induced after allergic poly-sensitization can be prevented by mucosal but not by systemic administration of poly-peptides.
BACKGROUND
Patients with multiple sensitizations require alternative forms of treatment, as the efficacy of conventional immunotherapy is unsatisfactory.


OBJECTIVE
In the present study, we sought to compare the efficacy of a subcutaneously (s.c.) and a mucosally applied polyvalent vaccine to reduce allergic immune responses within airway and lung tissues.


METHODS
Female BALB/c mice were intraperitoneally immunized with recombinant (r)Bet v 1, rPhl p 1 and rPhl p 5, followed by an aerosol challenge of birch and phleum pollen extract. For tolerance induction, either a mixture of the immunodominant peptides or a hybrid peptide of the respective antigens was s.c. injected or intranasally applied before poly-sensitization.


RESULTS
Mucosal but not systemic pre-treatment with poly-peptides led to significant suppression of eosinophils and IL-5 production in bronchoalveolar lavages, as well as IL-5, IL-4, IL-13 and eotaxin levels in lung cell cultures. Lung histology showed a clear reduction of cellular infiltration and mucus production only in intranasally pre-treated mice. In accordance, also the systemic immune response, characterized by IgE-dependent basophil degranulation and IL-4 levels in vitro, was significantly reduced by mucosal antigen application, but only marginally influenced by subcutaneous pre-treatment. Both treatment routes led to up-regulated CTLA4 expression in splenocytes, whereas only after mucosal pre-treatment Foxp3 expression levels were enhanced in lung CD3(+) T cells. Furthermore, intranasal but not subcutaneous application of the peptides enhanced IL-10 levels in the lungs, indicating regulatory mechanisms operating in local tolerance induction.


CONCLUSIONS
Mucosal application of peptides is superior to systemic application in preventing both local and systemic poly-allergic T helper2 immune responses, suggesting mucosal tolerance induction as an attractive strategy for the primary and secondary prevention of allergic multi-sensitization and lung pathology.
Hufnagl
K
K
Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Focke
M
M
Gruber
F
F
Hufnagl
P
P
Loupal
G
G
Scheiner
O
O
Wiedermann
U
U
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003888:Desensitization, Immunologic; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D011058:Pollen / Q000276:immunology; D051381:Rats; D012137:Respiratory System / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D010455:Peptides