Effect of intranasal fluticasone on cellular infiltration, endothelial adhesion molecule expression, and proinflammatory cytokine mRNA in nasal polyp disease
Hamilos, DL; Thawley, SE; Kramper, MA; Kamil, A; Hamid, QA
| HERO ID | 1514889 |
|---|---|
| In Press | No |
| Year | 1999 |
| Title | Effect of intranasal fluticasone on cellular infiltration, endothelial adhesion molecule expression, and proinflammatory cytokine mRNA in nasal polyp disease |
| Authors | Hamilos, DL; Thawley, SE; Kramper, MA; Kamil, A; Hamid, QA |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 103 |
| Issue | 1 Pt 1 |
| Page Numbers | 79-87 |
| Abstract | <strong>BACKGROUND: </strong>Nasal polyp (NP) disease demonstrates a gradual response to treatment with intranasal steroids. We hypothesized that various inflammatory features that promote NP eosinophilia would show a differential sensitivity to treatment with intranasal fluticasone.<br /><br /><strong>OBJECTIVES: </strong>We conducted a double-blind, placebo-controlled trial of 4 weeks of intranasal fluticasone propionate or matching placebo to assess their effectiveness in reducing NP inflammatory cells, expression of endothelial vascular cell adhesion molecule (VCAM)-1 and P-selectin, and expression of cytokines involved in induction of a group of adhesion molecules (ie, IL-4, IL-13, TNF-alpha, and IL-1beta).<br /><br /><strong>METHODS: </strong>Twenty subjects (9 women and 11 men) with severe chronic sinusitis and NP were studied. Systemic and intranasal steroids were withheld for a minimum of 1 month and 2 weeks, respectively, before the study. Biopsy specimens of NPs were obtained 1 week before and 4 weeks after treatment with intranasal fluticasone 100 microg or placebo per nostril administered twice daily. Biopsy specimens were snap frozen for immunostaining or fixed in paraformaldehyde for in situ hybridization. Pretreatment to posttreatment results were analyzed with Wilcoxon's signed-rank test.<br /><br /><strong>RESULTS: </strong>Fluticasone treatment significantly reduced NP eosinophilia (P =.02) and CD4(+) T lymphocytes (P =.02). Eosinophils expressing the marker EG2 were more significantly reduced (P =.007). Fluticasone also reduced the expression of P-selectin (P =.005) and the number of IL-4 and IL-13 mRNA+ cells (P =.02 and.05, respectively). In contrast, fluticasone did not significantly reduce expression of endothelial VCAM-1 or the number of TNF-alpha or IL-1beta mRNA+ cells in the polyps.<br /><br /><strong>CONCLUSIONS: </strong>We conclude that intranasal fluticasone reduced NP inflammation but that expression of proinflammatory cytokines and endothelial VCAM-1 were relatively unaffected by fluticasone treatment. These latter inflammatory features may contribute to the persistence of NP disease despite intranasal steroid treatment. |
| Doi | 10.1016/S0091-6749(99)70529-4 |
| Pmid | 9893189 |
| Wosid | WOS:000078112300013 |
| Url | https://linkinghub.elsevier.com/retrieve/pii/S0091674999705294 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Administration, Intranasal; Androstadienes/ administration & dosage; Anti-Inflammatory Agents/ administration & dosage; Blood Proteins/analysis; Double-Blind Method; Endothelium, Vascular/chemistry; Eosinophil Granule Proteins; Eosinophils/chemistry; Gene Expression/drug effects; Inflammation Mediators/analysis; Interleukin-13/genetics; Interleukin-3/genetics; Interleukin-4/genetics; Middle Aged; Myelin Basic Proteins/blood; Nasal Polyps/drug therapy/ pathology; P-Selectin/genetics; Peak Expiratory Flow Rate/drug effects; Placebos; RNA, Messenger/metabolism; Ribonucleases; Tumor Necrosis Factor-alpha/genetics; Vascular Cell Adhesion Molecule-1/ biosynthesis |