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

Abstract
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.
AuthorsQing Cai, Xiaoping Du, Bin Zhou, Chun Cai, Mohammad Habiby Kermany, Taijune Yoo
JournalORL; journal for oto-rhino-laryngology and its related specialties (ORL J Otorhinolaryngol Relat Spec) Vol. 71 Issue 3 Pg. 135-41 ( 2009) ISSN: 1423-0275 [Electronic] Switzerland
PMID19365153 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Cytokines
  • Tubulin
Topics
  • Administration, Oral
  • Animals
  • Autoimmune Diseases (drug therapy, immunology)
  • Cells, Cultured
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ear, Inner (immunology)
  • Evoked Potentials, Auditory, Brain Stem
  • Female
  • Hearing Loss (immunology)
  • Immune Tolerance (drug effects, immunology)
  • Immunization (methods)
  • Labyrinth Diseases (drug therapy, immunology)
  • Lymphocytes (cytology, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Spleen (cytology)
  • Tubulin (immunology, pharmacology)

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