Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis

Abstract

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

Keywords: IgA nephropathy; epipharyngeal abrasive therapy (EAT); interleukin 6 (IL-6); long COVID; myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); tumor necrosis factor alpha (TNFα).

Figure 1

Transnasal endoscopic photographs of the epipharynx under ordinary light and Narrow Band Imaging (NBI) mode in a patient with chronic epipharyngitis. (Left) panel shows the epipharynx pre-EAT treatment. (Right) panel shows the epipharynx following 2 months of treatment with EAT. The white arrow indicates severe mucosal swelling. The black arrow indicates cobblestone-like granular changes. The white arrowhead indicates submucosal bleeding. The black arrowhead indicates the temporary whitening phenomenon.

Figure 2

The distribution of Interleukin 6 (IL-6) mRNA (red dots; arrow heads), B cells (CD20+), T cells (CD3+), macrophages (CD68+), and vascular endothelial cells (CD34+) in the epipharynx of a patient with chronic epipharyngitis. Inserts in each image are magnified.

Figure 3

The mRNA expression patterns of Interleukin 6 (IL-6) in patient tissue samples without and with epipharyngeal abrasive therapy (EAT). (a) The representative pattern of IL-6 expression (brown dots) in the epipharynx of the EAT nontreated sample and the EAT-treated sample. Inserts in each image are magnified. (b) The details of IL-6 expression at the submucosal region of the EAT nontreated group (n = 8) and EAT-treated group (n = 11).

Figure 4

The mRNA expression patterns of tumor necrosis factor alpha (TNFα) in patient tissue samples without and with epipharyngeal abrasive therapy (EAT). TNFα (brown dots) in the epipharynx of the EAT nontreated sample (n = 1) and the EAT-treated sample (n = 1). Inserts in each image are magnified.

Figure 5

Epipharyngeal Abrasive Therapy (EAT). (a) The transnasal EAT technique using a 3D model (Nihon 3B Scientific Inc., Niigata, Japan). (b) The epipharynx during endoscopic EAT (E-EAT). The black arrow indicates a cotton swab.