Naked DNA encoding INF-γ enhances tubulin induced hearing loss in guinea pigs

Abstract

The purpose of this study is to delineate the immune injury mechanisms that involved in the autoimmune inner ear disease by introducing plasmid DNA encoding of TH1 cytokines (INF-γ) into the inner ear. β-Tubulin is a microtubular protein which we found as an important autoantigenic in Meniere's Disease as well as other autoimmune hearing loss. Hearing loss was induced in mice and guinea pigs when they are immunized with the tubulin molecules. Autoimmune hearing loss could be the results of TH1 cytokine responses from autoimmune injury. To test the hypothesis, guinea pigs were immunized with 200mg of tubulin in CFA and boosted once more. Two weeks later, we introduced 100ug (5ul) of naked DNA encoding INF-γ was injected into the left side inner ear through round window. Same volume of 0.1M PBS was injected into right side as control. ABR was recorded before and after the injection. 15 weeks after the injection, the animals were sacrificed and temporal bones were examined with H-E and INF-γ immunocytochemical staining. The ears injected with the plasmid DNA- INF-γ had an enhanced hearing loss (30 dB), and degeneration of the spiral ganglion was found in these ears. However, the injection of the naked DNA encoding INF-γ did not change the expression of the INF-γ in the inner ears. These results suggest that autoimmune hearing loss could be the result of TH1 responses to inner ear autoantigens.