Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer

Abstract

Interleukin-10 (IL-10) has an important role in the homeostatic regulation of autoreactive T-cell repertoire. We hypothesized that endogenous IL-10 would regulate the severity of b-tubulin-induced experimental autoimmune hearing loss (EAHL) and that exogenous IL-10 would abrogate it. BALB/c wild-type (WT) and homozygous IL-10-deficient mice (IL-10 À/À ) underwent b-tubulin immunization to develop EAHL; some IL-10 mice with EAHL were administered IL-10 DNA at the peak of EAHL. Auditory brainstem responses were examined over time. EAHL developed progressively in both WT and IL-10 À/À mice. However, the severity of hearing loss in the IL-10 À/À mice was significantly greater than that in WT animals. Moreover, disease severity was associated with a significantly enhanced interferon-g level and loss of hair cells in IL-10 À/À mice. IL-10 administered to EAHL IL-10 À/À mice promoted IL-10 expression. Consequently, hearing significantly improved by protecting hair cells in established EAHL. Importantly, IL-10 treatment suppressed proliferation of antigen-specific T-helper type 1 (Th1) cells, and the suppression can be attributed to inducing IL-10-secreting regulatory T cells that suppressed autoreactive T cells. We demonstrated that the lack of IL-10 exacerbated hearing loss, and the exogenous administration of IL-10 improved hearing. Mechanistically, our results indicate that IL-10 is capable of controlling autoimmune reaction severity by suppressing Th1-type proinflammatory responses and inducing IL-10-secreting regulatory T cells.

Biology and pathobiology of lipid droplets and their potential role in the protection of the organ of Corti

“…It has been suggested that interleukin-10 (IL-10) could be involved in controlling the level of the inflammatory response. In particular, autoimmune hearing loss is intensified in IL-10 deficient mice and this response is reversed by IL-gene transfer (Zhou et al, 2012), and the early phase of cochlear inflammation in a murine model, before the recruitment of leukocytes and macrophages, is significantly exacerbated by IL-10 deficiency (Woo et al, 2015). A second way to protect the auditory organ would be to enhance the resolution phase of inflammatory responses.…”

A network-based method using a random walk with restart algorithm and screening tests to identify novel genes associated with Menière's disease

“…IL10 is a cytokine synthesis inhibitory factor and a co-stimulator for the proliferation and differentiation of T and B mast cells [ 87 , 88 ]. For the relationships between IL10 and MD, although no direct relationships between such genes and the disease have been reported, a specific report on autoimmune hearing loss validated that the abnormal secretion of IL-10 may contribute to specific hearing loss symptoms of experimental autoimmune hearing loss [ 89 ]. Because hearing loss is a typical symptom of MD, which is also widely considered an autoimmune disorder, it is quite reasonable that IL10 may also participate in the pathological processes of MD [ 89 , 90 ].…”

Gene Therapy for Sensorineural Hearing Loss

“…Animal models of autoimmune hearing loss are generated by immunization with β-tubulin, one of the inner ear antigens (Cai et al 2009;Zhou et al 2011). In a study by Zhou et al (2012), autoimmune hearing loss was induced by immunization against β-tubulin in mice that are deficient in interleukin-10 (IL-10) (Zhou et al 2012). IL-10 is a cytokine ( Table 1) that mediates its anti-inflammatory actions by inhibiting the production of proinflammatory cytokines involved in monocyte/macrophage activation (Anderson et al 2004;Maynard & Weaver 2008).…”