Induction of tolerance by oral administration of beta-tubulin in an animal model of autoimmune inner ear disease.

Induction of peripheral tolerance by oral administration of low-dose beta-tubulin antigen may be an effective, antigen-specific method to suppress experimental autoimmune hearing loss. Five groups of mice were fed with phosphate-buffered saline (PBS), ovalbumin (OVA), 20, 30 or 200 microg of beta-tubulin, respectively. All mice were then immunized by beta-tubulin. Hearing thresholds were measured before and after immunization. Inner ear histology and cytokine profile were examined. Mice fed with 20 or 30 microg of beta-tubulin showed less hearing loss and less inner ear damage compared to the groups treated with PBS, OVA or 200 microg of beta-tubulin. Interferon-gamma (IFN-gamma) was decreased while interleukin-4 (IL-4), IL-5, IL-13 and TGF-beta were increased in both sera and in cell culture supernatants of the mice fed with 20 or 30 microg of beta-tubulin. However, no cytokine profile change was found in the group treated with 200 microg of tubulin. These results suggest that a low dose of beta-tubulin is active orally in an antigen-specific fashion and capable of inhibiting the autoimmune reactions in the inner ear by suppressing Th1 (IFN-gamma) and increasing Th2 and Th3 (IL-4, IL-5, IL-13 and TGF-beta) cytokines. Oral antigen tolerance may be used to treat autoimmune inner ear disease.