β-tubulin-induced autoimmune hearing loss exacerbates in IL-10-deficient mice and restores by IL-10 gene transfer (143.10)

Abstract IL-10 is a potent immunoregulatory cytokine in homeostatic regulation of autoreactive T cell repertoire, experimental autoimmune hearing loss (EAHL) is characterized by Th1 cell-mediated disorder plus down-regulation of IL-10. We hypothesized that endogenous levels of IL-10 function to regulate the severity of EAHL, and exogenous of IL-10 would abrogate EAHL. BALB/c (WT) and homozygous IL-10-deficient mice were underwent β-tubulin immunization to develop EAHL; some β-tubulin-immunized IL-10-deficient mice were intramuscular injected IL-10 DNA. EAHL developed progressively in both WT and IL-10-deficient mice immunized with β-tubulin, and severity of hearing loss in IL-10-/- mice was significantly greater than that in WT animals. However, the hearing function was significantly improved in IL-10 DNA administration group than that in the control group, ABR thresholds are equivalent to naive controls, and histological analysis of cochlear cross section was similar to those of naïve controls. IL-10 DNA administration suppressed autoreactive T cells and reduced expression of IFN-γ, the proportion of regulatory T cells (Treg) of IL-10-treated mice was significantly increased in comparison with control mice. Therefore lack of IL-10 exacerbates hearing loss, exogenous administration of IL-10 improved hearing function. Thus, IL-10 is capable of controlling autoimmune reaction severity by suppressing Th1-type inflammatory production and enhancing the percentage of Treg cells.