Oral administration of specific antigens to allergy-prone infant dogs induces IL-10 and TGF-beta expression and prevents allergy in adult life.
BACKGROUND
Oral administration of allergens can induce immune tolerance to specific allergens in rodents and hence might be a possibility to prevent and treat allergic diseases in human subjects. However, the gastrointestinal tract of mice is different from that of human subjects. The absorption of specific antigens and subsequent antigen presentation to intestinal T cells is different in both species, making it difficult to extrapolate results.


OBJECTIVE
We investigated primary oral tolerance to ovalbumin (OVA) in an IgE high-responder dog model, which is more predictive for human allergic diseases than corresponding rodent models.


METHODS
Oral tolerance was induced by means of a 28-day treatment with OVA dissolved in cow's milk.


RESULTS
We observed reduced OVA-specific IgE and IgG production in response to ensuing subcutaneous challenges. Allergic conjunctivitis induced by means of ocular and airway provocation was significantly reduced in tolerized animals compared with that seen in nontolerized control animals. In addition, eosinophilia and neutrophilia in bronchoalveolar lavage fluid and bronchoconstriction after airway allergen challenge were significantly suppressed in tolerized animals. Cytokine analysis by means of real-time PCR on bronchoalveloar fluid cells after allergen challenge revealed a high-level expression of IL-10 and transforming growth factor beta, predominantly in the CD14(+) population.


CONCLUSIONS
Feeding infant beagles with OVA for 4 weeks is sufficient to prevent hallmark manifestations of asthma and allergy in adult life. The mechanism of oral tolerance involved an increased expression of IL-10 and transforming growth factor beta cytokines.
Novartis Research Institute, Vienna, Austria.
Barbara
B
Zemann
Christoph
C
Schwaerzler
Monika
M
Griot-Wenk
Marijke
M
Nefzger
Peter
P
Mayer
Heinz
H
Schneider
Alain
A
de Weck
José M
JM
Carballido
Ekke
E
Liehl
D000284:Administration, Oral; D000818:Animals; D001249:Asthma / Q000517:prevention & control; D003231:Conjunctivitis / Q000517:prevention & control; D004285:Dogs; D006967:Hypersensitivity / Q000517:prevention & control*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics*; D010047:Ovalbumin / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics*
D007074:Immunoglobulin G; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E; D010047:Ovalbumin