Low-protein diet induces oral tolerance to ovalbumin in mice.

ABSTRACT

The suitable development of oral tolerance against ingested dietary foods is of critical importance to escaping food allergy. Using mice as an animal model for oral tolerance against ovalbumin (OVA) as a dietary antigen, we investigated the effects of dietary protein on their immunological tolerance. Female BALB/c mice fed either a 20% or 5% protein diet were orally administered 5 mg of OVA for four consecutive days, then immunized intraperitoneally with 100 microg of OVA. The immunized group of mice were fed and treated in the same manner, except that they received orally distilled water for four consecutive days before receiving intraperitoneal immunization with the antigen. Immunization alone with OVA elevated the total IgE and induced the production of OVA-specific antibodies IgE, IgG, IgG1, and IgG2a in the sera of both the 20% and 5% protein diet groups. The oral administration of OVA to mice before intraperitoneal immunization significantly reduced the total IgE and OVA-specific antibodies in mice fed 5% protein diet, but it had hardly any effect on those in mice fed a 20% protein diet. When spleen cells from these groups of mice were cultured with OVA as a mitogen, they responded substantially to OVA in the immunized groups fed 20% and 5% protein diets and in the presensitized group fed 20% protein, but those from the presensitized group fed a 5% protein diet did not respond. Furthermore, when IL-4 was assayed in the spleen cell cultures of the 20% and 5% groups, mice in the presensitized group fed a 5% protein diet produced a significantly less amount of IL-4 than those fed a 20% protein diet. Moreover, irrelevant to the protein amount in the diet, the production of IFN-gamma from spleen cell cultures dramatically decreased in the group without presensitization and profoundly increased in the presensitized group of mice fed a 5% protein diet. These findings suggest that a low-protein diet leads to an induction of oral tolerance against dietary antigens; this appears to involve a clear down-regulation of Th2 cytokine, IL-4.