The Role of Cytokines in Modulating Vocal Fold Fibrosis: A Contemporary Review

Abstract

Objectives Vocal fold (VF) scarring and laryngeal stenosis are a significant clinical challenge. Excessive scar formation causes low voice quality or even life‐threatening obstructions. Cytokines are thought to modulate multiple steps of the establishment of VF fibrosis, but there is no systematic report regarding their role in modulating VF fibrosis. This review aims to investigate the role of cytokines in modulating vocal fold fibrosis. Study Design Literature review. Methods This review searched for all relevant peer publications in English for the period 2009 to 2019 in the PubMed database using search terms: “laryngeal stenosis,” “vocal fold scarring,” and “cytokines.” A thorough investigation of the methods and results of the reviewed studies was performed. Results Comprehensive research in various studies, including analyses of prostaglandin E2 (PGE2), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), transforming growth factor‐β3 (TGF‐β3), and interleukin‐10 (IL‐10), supports cytokine therapy for VF scarring and laryngeal stenosis to some extent. A few clinical studies on this topic support the conclusion that HGF and bFGF can be selected as effective drugs, and no serious side effects were found. Conclusions This review describes the potential of cytokines for modulating the process of VF fibrogenesis, although cytokines are still an unproven treatment method. As no ideal drugs exist, cytokines may be considered the candidate treatment for preventing VF fibrogenesis. Laryngoscope, 131:139–145, 2021

Human amniotic epithelial cell transplantation improves scar remodeling in a rabbit model of acute vocal fold injury: a pilot study

“…It is documented that this is one of the mechanisms by which COL1 increases the angiogenic potential of the endothelial cells [52]. Notably, HGF has established antifibrotic efficacy in vocal fold wound healing in both in vitro and in vivo studies [53,54].…”

Current approaches to management of vocal fold scar

“…This is an area of much research. Xu and Fan reviewed the role of cytokines in modulating VF scarring [14 ▪ ]. They identified several different molecules with positive effects on VF healing [14 ▪ ].…”

Scarless Healing of Injured Vocal Folds Using an Injectable Hyaluronic Acid-Waterborne Polyurethane Hybrid Hydrogel to Tune Inflammation and Collagen Deposition

“…VF scarring, one of the main reasons for long-lasting dysphonia, results from injury to the unique layered structure of the VFs. − The main features of VF scarring are disorganized elastin bundles and collagen, loss of important extracellular matrix (ECM) constituents, volume deficiency, decreased pliability, and glottal insufficiency. , Patients with scarred VFs, whether congenitally (sulcus vocalis) or acquired (phonosurgery, traumas, infection, radiation, iatrogenic reasons, etc. ), suffer from symptoms of vocal fatigue, breathy voice, difficulty in sustaining tone, and even progress to life-threatening airway obstruction; those symptoms usually negatively affect their daily life and social interactions, causing them to miss work or change occupations, and some even cause psychological problems …”

“…), suffer from symptoms of vocal fatigue, breathy voice, difficulty in sustaining tone, and even progress to lifethreatening airway obstruction; 6 those symptoms usually negatively affect their daily life and social interactions, causing them to miss work or change occupations, and some even cause psychological problems. 7 Treatment of scarred VF includes voice therapy, scar excision, localized steroid injection, and biomaterial injection or implantation. 8 Although voice therapy is non-invasive, the duration is usually long and requires the cooperation of patients.…”