title: A new model of laryngitis: neuropeptide, cyclooxygenase, and cytokine profile.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Lima-Rodrigues
authors.forename: Ana
authors.initials: A
authors.lastname: Valle-Fernandes
authors.forename: Nuno
authors.initials: N
authors.lastname: Lamas
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruz
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.forename: Fernanda
authors.initials: F
authors.lastname: Milanezi
authors.forename: Rui
authors.initials: R
authors.lastname: Nunes
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
authors.forename: Jorge
authors.initials: J
authors.lastname: Pedrosa
authors.forename: António G
authors.initials: AG
authors.lastname: Castro
authors.forename: Armando
authors.initials: A
authors.lastname: Almeida
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000032:analysis*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007441:Intubation, Gastrointestinal; D007820:Laryngeal Mucosa / Q000473:pathology*; D007827:Laryngitis / Q000209:etiology*; D008297:Male; D008565:Membrane Proteins; D009475:Neurons, Afferent / Q000473:pathology; D009479:Neuropeptides / Q000032:analysis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008565:Membrane Proteins; D009479:Neuropeptides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013373:Substance P; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015740:Calcitonin Gene-Related Peptide