Tu43 - NaCl Exposure Results in Increased Expression and Processing of IL-1β in Meniere's Disease Patients

Meniere's disease (MD) causes fluctuating hearing loss, aural fullness and episodic vertigo.  Initial management of MD is a low sodium diet and use of diuretics.  A subset of MD patients have an autoimmune etiology.  Recent autoimmune disease literature suggested that high sodium salt intake causes inflammation resulting in a higher risk and clinical worsening. Our previous studies have demonstrated elevated interleukin-1β (IL-1β) levels in corticosteroid-unresponsive autoimmune inner ear disease (AIED) patients and hearing could be improved with use of an interleukin-1 receptor antagonist anakinra. We recently identified that patients with AIED uniquely process IL-1β to a 28kDa form that is biologically active and proinflammatory. In this study, we characterized the production, processing and release of the pro-inflammatory cytokines IL-1 and IL-6 from PBMC of MD patients in response to sodium chloride (NaCl).  We also queried whether diuretics, corticosteroids or anakinra could alter pro-inflammatory cytokine expression in patients with MD. We observed that MD patients showed processing of IL-1β to the 28kDa product in peripheral blood mononuclear cells (PBMC) when cultured in high sodium salt (NaCl) culture environment, and that this product is abrogated with diuretic triamterene-hydrochlorothiazide

(T-HCTZ). Studies are underway to characterize which cell type in PBMC is majorly responsible for processing of IL-1β to the 28kDa.