Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: development of tolerance using environmental antigens.
BACKGROUND
Studies show that children in rural environments develop less asthma and allergic rhinitis than their urban counterparts. This may be a result, in part, of neonatal exposure to environmental antigens such as LPS and/or early exposure to allergens.


OBJECTIVE
This study examined the effects of neonatal allergen and/or LPS exposure on subsequent immune responses to allergen.


METHODS
Newborn mice were exposed to LPS and/or ovalbumin. At age 6 weeks, these animals were sensitized and challenged with ovalbumin, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed.


RESULTS
Animals exposed to LPS in the neonatal period developed T cells expressing CD25 and IL-10 on sensitization and challenge. They demonstrated abrogation of airway hyperresponsiveness and significant decreases in IL-13 from bronchoalveolar lavage fluid and in specific IgE. IL-4-expressing spleen cells were also significantly decreased. Mice exposed in the neonatal period to ovalbumin demonstrated airway hyporesponsiveness after subsequent ovalbumin sensitization and challenge and did not produce specific IgE. In contrast, these animals showed increases in IFN-gamma. Animals exposed to both LPS and ovalbumin developed a response characterized by IL-10 and IFN-gamma-expressing T cells.


CONCLUSIONS
This suggests that mucosal antigen exposure in the neonatal period results in inhibition of allergic responses to environmental allergens. Early LPS exposure directs mucosal responses toward tolerance, whereas ovalbumin exposure follows the T(H)1-type response on subsequent sensitization.


CONCLUSIONS
This study suggests that prevention of airways allergy may be best achieved by appropriate exposure of the airway mucosa early in life to environmental antigens.
Wang
Yufa
Y
Meakins-Christie Laboratories, 3626 St Urbain, Montreal, Quebec H2X 2P2, Canada.
McCusker
Christine
C
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D004777:Environment; D005260:Female; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000517:prevention & control*; D006255:Rhinitis, Allergic, Seasonal / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000485:Allergens; D016207:Cytokines; D008070:Lipopolysaccharides; D016753:Interleukin-10; D010047:Ovalbumin