Oral administration of endotoxins modulates allergen-induced immune reactions in a rat model of food allergy

Abstract

Background The “hygiene hypothesis” postulates that a lack of immune stimulation early in life due to increasingly “sterile” living conditions in western countries augments the development of Th2-skewed immune responses to environmental allergens. Accordingly, immune modulating intervention in this period of life may be most favorable for preventive strategies against the development of allergic diseases. Aim Aim of the current study was to test the effects of oral administration of endotoxin in a rat model of food allergy. Methods Brown Norway rats were sensitized ip with ovalbumin (OVA) combined with pertussis and Al(OH)2 as adjuvans on days 35, 40 and 45. On days 60 and 61, rats were locally challenged with OVA by gavage feeding. Different amounts of endotoxin or PBS were administered orally, first once daily (days 7–21 post partum), than every third day up to an age of 42 days. Results Detection of increased allergen specific Ig serum levels and proliferative responses of spleen MNC confirmed successful systemic sensitization to OVA, but did not reveal significant differences between endotoxin and PBS-treated rats. In contrast, increased numbers of total lymphocytes and activated T-cells with enhanced in vitro IFN-γ and IL-10 cytokine production were detected in mesenteric lymph nodes (MLN) of endotoxin-, compared to PBS-treated rats. These observations were strongly dependent on the amount of administered endotoxin and only occurred with dosages above 0,2 ng/kg/day. Conclusion These data suggest that local administration of endotoxin in the intestine exhibits immune modulating effects with increased Th1 and T regulatory responses in a dose-dependent manner.