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.
Department of Medicine, Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
Qing
Q
Cai
Xiaoping
X
Du
Bin
B
Zhou
Chun
C
Cai
Mohammad Habiby
MH
Kermany
Taijune
T
Yoo
D000284:Administration, Oral; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner / Q000276:immunology; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D034381:Hearing Loss / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007114:Immunization / Q000379:methods; D007759:Labyrinth Diseases / Q000188:drug therapy* / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D014404:Tubulin / Q000276:immunology / Q000494:pharmacology*
D016207:Cytokines; D014404:Tubulin