Effect of ultrafine zinc oxide (ZnO) nanoparticles on induction of oral tolerance in mice.

Ultrafine nanoparticles of zinc oxide (ZnO) recently became available as a substitute for larger-size fine ZnO particles. However, the biological activity of ultrafine ZnO currently remains undefined. In the present study, we investigated the effect of ultrafine ZnO on oral tolerance that plays an important role in the prevention of food allergy. Oral tolerance was induced in mice by a single oral administration (i.e., gavage) of 25 mg of ovalbumin (OVA) 5 days prior to a subcutaneous immunization with OVA (Day 0). Varying doses of ultrafine (diameter: approximately 21 nm) as well as fine (diameter: < 5 microm) ZnO particles were given orally at the same time during the OVA gavage. The results indicated that a single oral administration of OVA was followed by significant decreases in serum anti-OVA IgG, IgG(1), IgG(2a), and IgE antibodies and in the proliferative responses to the antigen by these hosts' spleen cells. The decreases in these immune responses to OVA were associated with a marked suppression of secretion of interferon (IFN)gamma, interleukin (IL)-5, and IL-17 by these lymphoid cells. Treatment with either ultrafine or fine ZnO failed to affect the oral OVA-induced suppression of antigen-specific IgG, IgG(1), IgG(2a), and IgE production or lymphoid cell proliferation. The suppression induced by the oral OVA upon secretion of IFN gamma, IL-5, and IL-17 was also unaffected by either size of ZnO. These results indicate that ultrafine particles of ZnO do not appear to modulate the induction of oral tolerance in mice.