IL‐11 and IL‐17 expression in nasal polyps: Relationship to collagen deposition and suppression by intranasal fluticasone propionate
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Résumé
OBJECTIVES/HYPOTHESIS: Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features. STUDY DESIGN: Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression. METHODS: Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means. RESULTS: Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance. CONCLUSION: NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle