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N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients

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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.

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Abbreviations

AIED:

Autoimmune inner ear disease

NAC:

N-Acetyl-l-cysteine

GSH:

l-γ-Glutamyl-l-cysteinyl-glycine

ROS:

Reactive oxygen species

MPO:

Myeloperoxidase

TPO:

Thyroperoxidase

EAE:

Experimental autoimmune encephalomyelitis

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Acknowledgments

This study was supported by a National Institutes of Health grant R21/R33DC011827 (AV) and Merrill & Phoebe Goodman Otology Research Center.

Author Contributions

The experiments were conceived and designed by SP and AV. The experiments were performed by SP and CS. The data were analyzed by SP and AV. AV contributed reagents/materials/analysis tools; SP and AV wrote the paper.

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Authors and Affiliations

  1. The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA

    Shresh Pathak, Corey Stern & Andrea Vambutas

  2. The Apelian Cochlear Implant Center, Department of Otolaryngology, North Shore-LIJ Health System, New Hyde Park, NY, USA

    Andrea Vambutas

  3. Department of Otolaryngology, Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, NY, USA

    Shresh Pathak & Andrea Vambutas

  4. Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, NY, USA

    Andrea Vambutas

  5. Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Shresh Pathak & Andrea Vambutas

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  1. Shresh Pathak
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  2. Corey Stern
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  3. Andrea Vambutas
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Correspondence to Andrea Vambutas.

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Conflict of interest

Dr. Vambutas, the Feinstein Institute for Medical Research, holds a patent application for the use of IL-1β receptor antagonists for the treatment of AIED and related diseases.

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Pathak, S., Stern, C. & Vambutas, A. N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients. Immunol Res 63, 236–245 (2015). https://doi.org/10.1007/s12026-015-8696-3

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