title: N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients.
abstract: Autoimmune inner ear disease (AIED) is a poorly understood disease marked by bilateral, rapidly progressive hearing loss triggered by unknown stimuli, which is corticosteroid responsive in 60 % of patients. Although the mechanism of the disease is not precisely understood, a complex interaction of cytokines is believed to contribute toward the inflammatory disease process and hearing loss. Previously, we showed the role of TNF-α in steroid-sensitive and IL-1β in steroid-resistant immune-mediated hearing loss. N-Acetylcysteine (NAC), a broad spectrum antioxidant, has been effective in other autoimmune disorders. Other studies have shown NAC to have a protective adjunct role in human idiopathic sudden hearing loss, where the addition of NAC resulted in better hearing recovery than with steroids alone, although the mechanism of this protection was not elucidated. In the present study, we observed PBMCs from AIED patients exhibited higher baseline TNF-α and MPO levels compared with normal healthy controls. NAC effectively abrogates LPS-mediated TNF-α release from PBMC of both AIED patients and controls. We demonstrated that in AIED patients, the TNF-α downstream signaling pathway appears aberrantly regulated, influencing both MPO and IL-8 expression. Given that NAC effectively abrogated LPS-mediated TNF-α release and exerted minimal effects on the downstream targets of this pathway, we feel NAC may be a rational adjunct therapy for this enigmatic disease, worthy of clinical exploration.
authors.affiliation: The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.|Department of Otolaryngology, Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, NY, USA.|Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Shresh
authors.initials: S
authors.lastname: Pathak
authors.affiliation: The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Stern
authors.affiliation: The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA. vambutas@nshs.edu.|The Apelian Cochlear Implant Center, Department of Otolaryngology, North Shore-LIJ Health System, New Hyde Park, NY, USA. vambutas@nshs.edu.|Department of Otolaryngology, Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, NY, USA. vambutas@nshs.edu.|Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, NY, USA. vambutas@nshs.edu.|Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. vambutas@nshs.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vambutas
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007759:Labyrinth Diseases / Q000188:drug therapy* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D058990:Molecular Targeted Therapy; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D000111:Acetylcysteine
keywords: Autoimmune inner ear disease (AIED); Myloperoxidase (MPO); N-Acetylcysteine (NAC); Tumor necrosis factor alpha (TNF-α)