Modulation of oral tolerance to ovalbumin by dietary protein in mice

This study sought to determine whether oral tolerance to ovalbumin (OVA), responsible for food allergy, is affected by different amounts of protein intake. For this, 6-wk-old BALB/c mice were fed with low protein (5%, LP), normal protein (20%, NP) and high protein (40%, HP) diets, orally given either OVA (OVA-fed) or water (Water-fed) for 4 d, and then immunized intraperitoneally twice at a 3-wk interval with alum-precipitated OVA. After the last immunization, sera were collected to measure total and OVA-specific IgE by enzyme assay (ELISA). Splenocytes were cultured and stimulated with concanavalin A (Con A), lipopolysaccharide (LPS) or OVA and assayed for 3H-thymidine incorporation. The culture supernatants from their splenocytes stimulated with OVA were analyzed for interleukin (IL)-4, interferon (IFN)-gamma, and IL-12. Total IgE was significantly higher in OVA-fed HP groups as compared to NP and LP groups (p<0.05). The highest and the lowest OVA-specific IgE were observed in HP and LP diet groups, respectively (p<0.05). OVA-fed mice receiving the LP diet demonstrated significantly lower IL-4 as compared to the other two groups (p<0.05), while IFN-gamma was significantly higher in the LP compared to the HP group (p<0.05). Levels of IL-12 did not differ among the OVA-fed groups. Splenocytes of OVA-fed mice kept on the LP and HP diet showed significant impairment of proliferation to OVA as compared to the NP group (p<0.01). Proliferation against Con A was impaired in the LP group compared to the NP group (p<0.05) but not in Water-fed groups. However, it was higher against LPS in the HP than the LP group (p<0.05) both in Water-fed and OVA-fed animals. All these findings indicate that established oral tolerance to OVA is clearly affected by the amount of protein diet. They support the suggestion that dietary protein plays an important role(s) in IgE-mediated food allergies.