Effect of betahistine on pro-inflammatory cytokine expression in autoimmune inner ear disease and Meniere's disease patients

Objective: Betahistine is a partial H1 receptor agonist and a potent H3 receptor antagonist commonly used for the treatment of MD and peripheral vertigo. The aim of this study was to investigate the impact of betahistine on the salt induced cytokine expression profiles of AIED and MD patients. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with autoimmune inner ear disease (AIED) or Meniere's disease (MD) during an acute exacerbation of hearing loss. These PBMCs were cultured with 80 mM NaCl or a combination of 80 mM NaCl and betahistine and IL-1 beta and IL-6 expression were measured by real time PCR and ELISA. Results: In most patients, IL-1 beta expression in response to NaCl exceeded the unstimulated condition and this expression was abrogated by the addition of betahistine, which was statistically significant at p = .004. mRNA expression of IL-1 beta was not reduced when samples were treated with both salt and betahistine compared to samples treated with salt alone, inferring the mechanism of betahistine-mediated IL-1 beta suppression is post-translational. Similarly, IL-6 cellular release was augmented with salt exposure and reduced with co-culture of betahistine. Unlike IL-1 however, betahistine appeared to reduce IL-6 mRNA expression. Conclusion: We observe that betahistine abrogates salt-induced IL-1 beta expression, suggesting an additional treatment option for AIED and MD patients with inflammatory mediated disease.