Pepsin-induced Differential IL-6 Expression in Laryngeal and Laryngopharyngeal Tissue: Non-invasive Rat Model for Laryngopharyngeal Reflux

Adelien, Adelien; Irfannuddin, Irfannuddin; Darmawan, Hardi; Surono, Agus; Murti, Krisna; Harahap, Debby Handayati; Zulka, Elvie

doi:10.22038/ijorl.2026.93308.4101

Pepsin-induced Differential IL-6 Expression in Laryngeal and Laryngopharyngeal Tissue: Non-invasive Rat Model for Laryngopharyngeal Reflux

Articles in Press

Document Type : Original

Authors

¹ Department of Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine, Sriwijaya Universty Indonesia.

² Department of Physiology, Faculty of Medicine, Sriwijaya University Indonesia.

³ Department of Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine, Gadjah Mada University Indonesia.

⁴ Department of Anatomical Pathology, Faculty of Medicine, Sriwijaya University Indonesia.

⁵ Department of Pharmacology, Faculty of Medicine, Sriwijaya University Indonesia.

⁶ Department of Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine, Sriwijaya University Indonesia.

10.22038/ijorl.2026.93308.4101

Abstract

Introduction:
Laryngopharyngeal reflux is a common condition caused by exposure of the upper aerodigestive tract to gastroduodenal content, resulting in inflammation to the area. Despite the condition being well documented in the human population, the literature on animal models for laryngopharyngeal reflux is currently limited. The aim of this study is to create a non-invasive model of laryngopharyngeal reflux using rats to investigate changes in IL-6 expression in the laryngeal and laryngopharyngeal regions.
Materials and Methods:
Male Wistar rats, ranging from ages 10-14 weeks, were exposed to 0.5% bovine pepsin dissolved in artificial gastric juice three times daily for 5-15 days via a modified IV cannula in several volumes (0 mL, 0.1 mL, 0.15 mL, and 0.2 mL) according to the treatment groups. Subsequently, laryngeal and laryngopharyngeal tissue IL-6 concentrations were measured through ELISA on allotted days of sacrifice.
Results:
Significant differences in laryngeal and laryngopharyngeal tissue IL-6 concentration were measured (p = 0.005 and p = 0.020 respectively). Laryngeal expression of IL-6 was related to the volume administered (p = 0.007) but not to the duration of exposure (p = 0.338), with no significant interaction between duration of exposure and administered volume (p = 0.515). On the other hand, laryngopharyngeal expression of IL-6 was related to the duration of exposure (p< 0.001) but not to the volume administered (p = 0.521) with significant interaction between duration and volume (p < 0.001).
Conclusion:
The study established the feasibility of using a non-invasive rat model for studying laryngopharyngeal reflux. Additionally, the study demonstrated the differential responses of IL-6 to the addition of the acid-pepsin insult, with dose-dependent IL-6 responding more in laryngeal tissue and time-dependent IL-6 responding in laryngopharyngeal tissue.

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