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Keywords:

  • Laryngeal inflammation;
  • neuropeptides;
  • cyclooxygenase-2;
  • cytokines;
  • nasogastric intubation;
  • immunocytochemistry;
  • mRNA expression;
  • reverse-transcriptase polymerase chain reaction analysis;
  • animal model

Abstract

Objectives/Hypothesis: To develop and characterize a new model of laryngeal inflammation by analyzing the presence of neurogenic peptides and expression of cyclooxygenases (COX) and cytokines in the mucosa.

Study Design: Laryngitis induced by nasogastric intubation (NGI) was evaluated by histopathologic changes of the mucosa, alterations in calcitonin gene related peptide (CGRP) and substance P (SP) neuropeptides in sensory fibers, and COX-1,2, and cytokine (interleukin [IL]-1, IL-6, IL-10, tumor necrosis factor [TNF]-α) expression in the laryngeal mucosa.

Methods: Rats submitted to NGI for 1 to 5 weeks were compared with controls. Laryngeal sections were immunostained for stereologic analysis of SP and CGRP fiber density and number of mucosal cells expressing COX-2. Alterations in inflammatory mediators were evaluated by quantitative reverse-transcriptase polymerase chain reaction.

Results: NGI induced metaplasia of the epithelium and narrowing of the laryngeal lumen because of hypertrophy of laryngeal glandules and edema. An initial decrease in CGRP- and SP-immunoreactive fibers in the laryngeal mucosa (1–3 wk) was reverted with time (5 wk). COX-2 expression in mucosal cells increased progressively, reaching a maximum level at 5 weeks, and was observed in mononuclear immune cells, which is indicative of a chronic inflammatory process. In regard to mRNA expression levels of inflammatory mediators, TNF-α was increased during the 5 week NGI, and IL-10 decreased during the 5 weeks,whereas IL-1β, IL-6, and COX-2 increased in the first 1 to 2 weeks and returned to baseline at 5 weeks.

Conclusions: This NGI model results in laryngeal chronic inflammation without direct mechanical aggression of the mucosa and may contribute to the study of future therapeutic approaches to this pathology.