A new model of laryngitis: neuropeptide, cyclooxygenase, and cytokine profile

Laryngoscope. 2008 Jan;118(1):78-86. doi: 10.1097/MLG.0b013e3181492400.

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]-[alpha]) 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-[alpha] was increased during the 5 week NGI, and IL-10 decreased during the 5 weeks,whereas IL-1[beta], 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / analysis
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cytokines / analysis*
  • Disease Models, Animal
  • Inflammation Mediators / analysis
  • Interleukin-10 / analysis
  • Interleukin-1beta / analysis
  • Interleukin-6 / analysis
  • Intubation, Gastrointestinal
  • Laryngeal Mucosa / pathology*
  • Laryngitis / etiology*
  • Male
  • Membrane Proteins
  • Neurons, Afferent / pathology
  • Neuropeptides / analysis*
  • Prostaglandin-Endoperoxide Synthases / analysis*
  • Rats
  • Rats, Wistar
  • Substance P / analysis
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Membrane Proteins
  • Neuropeptides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Substance P
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat
  • Ptgs2 protein, rat
  • Calcitonin Gene-Related Peptide