A new model of laryngitis: neuropeptide, cyclooxygenase, and cytokine profile.
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.
Lima-Rodrigues
Manuel
M
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
Valle-Fernandes
Ana
A
Lamas
Nuno
N
Cruz
Andrea
A
Baltazar
Fátima
F
Milanezi
Fernanda
F
Nunes
Rui
R
Reis
Rui M
RM
Pedrosa
Jorge
J
Castro
António G
AG
Almeida
Armando
A
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
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