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: Shresh Pathak, Corey Stern, Andrea Vambutas
• Journal: Immunologic research (Immunol Res) Vol. 63 Issue 1-3 Pg. 236-45 (Dec 2015) ISSN: 1559-0755 [Electronic] United States
• PMID: 26392121 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Interleukin-8
• Tumor Necrosis Factor-alpha
• Peroxidase
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Antioxidants (pharmacology)
• Autoimmune Diseases (drug therapy, immunology)
• Humans
• Interleukin-8 (metabolism)
• Labyrinth Diseases (drug therapy, immunology)
• Leukocytes, Mononuclear (drug effects, immunology)
• Molecular Targeted Therapy
• Peroxidase (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)