Oral Administration of IL-12 Abrogates the Induction but Not the Maintenance of Oral Tolerance

Abstract

Background: IL-12 is a Th1-inducing cytokine and known to be induced by some food factors. This function of such foods is expected to be applied for antiallergic materials. However, the influence of IL-12 on the immune responses has not been fully investigated. Oral tolerance is an immunologically unresponsive state induced by orally administered food antigens. Although a failure in the induction of oral tolerance would result in food allergy, the mechanisms for the induction and abrogation of oral tolerance have not been clarified. IL-12 induced by food factors may also affect the induction of oral tolerance. In this study we examined the effect of the oral administration of IL-12 on the induction and maintenance of oral tolerance. Methods: BALB/c mice were fed β-lactoglobulin with or without IL-12. After immunizing them with the antigen, the serum antibody titer of these mice was measured to evaluate the induction of oral tolerance. Results: The induction of oral tolerance was prevented in the mice that had been simultaneously fed the antigen and IL-12. On the other hand IL-12 did not abrogate the already established oral tolerance when it was administered after feeding the antigen. We also found that oral tolerance could be induced normally in mice that had failed to induce such tolerance by simultaneous feeding of IL-12 and the antigen. Conclusions: The results indicate that IL-12 induced in the intestine by some food factors is involved in the regulation of oral tolerance.

Oral Administration of Alginic Acid Oligosaccharide Suppresses IgE Production and Inhibits the Induction of Oral Tolerance

“…9) We conclude from all this evidence that ALGO can be used as a novel anti-allergic food material, although it also has a negative function of inhibiting the induction of oral tolerance, because this risk is very low. BALB/c mice were fed five times with 10 mg each of ALGO.…”

“…8) We have reported that oral administration of IL-12 abrogated the induction of oral tolerance to an antigen fed simultaneously with IL-12. 9) This evidence indicates that not only IL-12 but also some food factors abrogated the induction of oral tolerance, suggesting that such food factors are a trigger for hypersensitivity to food antigens. If ALGO also inhibits the induction of oral tolerance, that is a negative indication for applying it as an anti-allergic food.…”

“…9) We considered that ALGO would also affect oral tolerance through IL-12, because IL-12 is a critical factor induced by ALGO in inhibiting IgE production. 4) Our results in this study suggest strongly that some food factors which induce IL-12 and can be expected to have anti-allergic, anti-tumor, and anti-virus activity would inhibit the induction of oral tolerance.…”