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Fluticasone propionate downregulates nasal fibroblast functions involved in airway inflammation and remodeling.

Silvestri M, Sabatini F, Scarso L, Cordone A, Dasic G, Rossi GA.

Pulmonary Department, Giannina Gaslini Institute, Genoa, Italy.

BACKGROUND: Besides being highly effective in the treatment of allergic and nonallergic rhinitis with eosinophilia, intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. We evaluated the ability of fluticasone propionate to downregulate fibroblast functions related to nasal inflammation and remodeling. METHODS: Primary nasal polyp tissue-derived fibroblasts were stimulated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-4 or basic fibroblast growth factor (bFGF) in the presence of fluticasone propionate (0.1-100 nM). Fibroblast proliferation, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression and eotaxin release were then evaluated. RESULTS: As compared with unstimulated cultures, a significant increase in fibroblast proliferation was observed when the cells were stimulated with bFGF (p < 0.05), but not with TNF-alpha or IL-4 (p > 0.05). TNF-alpha induced an upregulation of ICAM-1 expression (p < 0.05), which was not seen in fibroblasts cultured in the presence of IL-4 or bFGF. No changes in VCAM-1 expression were induced by TNF-alpha, IL-4 or bFGF, whereas both TNF-alpha and IL-4 increased eotaxin release (p < 0.05). Both bFGF-induced fibroblast proliferation and TNF-alpha-induced ICAM-1 expression were significantly reduced by fluticasone, starting at the dose of 1 and 10 nM, respectively (p < 0.05). Fluticasone at concentrations of 1-100 nM effectively inhibited eotaxin release by TNF-alpha- or IL-4-stimulated fibroblasts (p < 0.05). CONCLUSIONS: The pharmacologic activity of fluticasone in patients with chronic upper airway inflammatory disease may include inhibition of resident fibroblast functions involved in airway inflammation and remodeling. Copyright 2002 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12037401&dopt=Abstract fluticasone Flonase



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Fluticasone inhibits the progression of allergen-induced structural airway changes.

Vanacker NJ, Palmans E, Pauwels RA, Kips JC.

Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium. nele.vanacker rug.ac.be

BACKGROUND: Inhaled corticosteroids are widely used as first-line therapy in patients with asthma. The concept of early introduction is more and more accepted. OBJECTIVE: In our rat model of airway remodelling, we investigated whether treatment with inhaled fluticasone propionate can inhibit further progression of established structural airway changes. METHODS: Sensitized Brown Norway rats were exposed to aerosolized ovalbumin (1%) from day 14 to 42. From day 28 to 42, animals were treated with inhaled fluticasone or placebo 30 min before each allergen challenge. One control group was exposed to PBS from day 28 to 42, a second control group throughout the whole experiment. RESULTS: Exposure to ovalbumin during 2 weeks induced structural airway changes, including epithelial cell proliferation, increase in airway wall area and fibronectin deposition. Goblet cell number was increased, although not significantly compared with PBS. Continuing allergen exposure for 2 weeks further enhanced each of these features. In addition, the amount of collagen in the airway wall was enhanced by 4 weeks allergen exposure compared with PBS-exposed animals. These additional increases were inhibited by treatment with fluticasone during the last 2 weeks. CONCLUSION: The progression of established allergen-induced structural airway changes in sensitized rats can be inhibited by treatment with fluticasone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12047439&dopt=Abstract fluticasone Flonase



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Intranasal fluticasone propionate inhibits allergen induced bone marrow eosinophilia in mice.

Sergejeva S, Tomaki M, Pullerits T, Zhao LL, Johnson M, Lotvall J.

The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Goteborg University, Gothenburg, Sweden.

Local corticosteroids are currently the most efficient safe anti-allergic treatment, which attenuate eosinophilic tissue inflammation through several mechanisms. We evaluated the effect of local airways corticosteroid on repeated allergen exposure-induced bone marrow activation and airway eosinophilia using the number of eosinophils in bone marrow, bronchoalveolar lavage fluid (BALf) and airways tissue as study end-points. Male BALB/c mice were sensitized by intraperitoneal injections of aluminum-precipitated ovalbumin (OVA) on two different days (5 days apart). Eight days after the second sensitization, the animals were challenged intranasally with OVA or phosphate-buffered saline (PBS) on 5 consecutive days. Concomitantly with challenges mice were treated with fluticasone propionate or respective vehicle. OVA exposures induced a significant increase in eosinophil numbers in bone marrow, BALf and airways tissue (P<0.005). Treatment with fluticasone propionate significantly reduced the increase of absolute number of mature bone marrow eosinophils (P=0.014) and showed a tendency towards decrease in the immature bone marrow eosinophil number (P=0.057) compared to controls. However, fluticasone propionate had no significant effect on BALf and airways tissue eosinophils (P=0.28 and 0.07, respectively). In this murine allergy model intranasal corticosteroid reduced number of bone marrow mature eosinophils, but did not significantly affect airways cell populations. Copyright 2002 Elsevier Science Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12090786&dopt=Abstract fluticasone Flonase



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Effect of topical fluticasone propionate on the mucosal allergic response induced by ragweed allergen and diesel exhaust particle challenge.

Diaz-Sanchez D, Tsien A, Fleming J, Saxon A.

Division of Clinical Immunology/Allergy, UCLA School of Medicine, Los Angeles, California 90095-1680, USA.

Glucocorticoids block the local allergic response in a variety of ways. However, studies have also shown that glucocorticoids increase in vitro IgE synthesis and that treatment with corticosteroids may result in elevated serum IgE concentrations. The ability of topical glucocorticoids to modulate the mucosal IgE response has not been elucidated. We studied the effect of topical steroid (fluticasone propionate) treatment on the local allergic antibody response induced by challenge with either allergen or diesel exhaust particles (DEP). A parallel group study was performed with ragweed-allergic subjects, each subject serving as his/her own control. Nasal provocation challenges were performed on three groups. One group received ragweed allergen, another diesel exhaust particles, and the third saline. The study was repeated following 1 week of treatment with intranasal fluticasone propionate. Each group received the same challenge as before. The concentrations of total immunoglobulins (IgE, IgG, IgA, and IgM), anti-ragweed antibody, IgE- and IgA-secreting cells, epsilon (epsilon) mRNA, and cytokine mRNAs (IL-2, -4, -5, -6, TNF-alpha, INF-gamma) were measured in nasal lavages performed before and at various time points after challenge. Treatment with fluticasone propionate for 7 days caused a decrease in the concentrations of nasal IgE protein, IgE-producing cells, total epsilon mRNA, and all the cytokine mRNAs tested. Furthermore, treatment with fluticasone propionate inhibited the production of allergen-specific IgE and cytokine mRNAs following challenge with ragweed antigen. However, fluticasone treatment did not significantly inhibit the enhancement of mucosal IgE production or cytokine mRNAs observed following nasal challenge with DEP. These results indicate that 1-week treatment with topical fluticasone propionate was effective in blocking local effects of allergen exposure but was unable to inhibit the adjuvant-like effect of DEP. Copyright 1999 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10075860&dopt=Abstract fluticasone Flonase



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Association of the Kobner phenomenon with disease activity and therapeutic responsiveness in vitiligo vulgaris.

Njoo MD, Das PK, Bos JD, Westerhof W.

Netherlands Institute for Pigmentary Disorders, Academic Medical Centre, Amsterdam. davidnjoo hotmail.com

OBJECTIVE: To investigate the association between the experimentally induced Kobner phenomenon (KP-e) and the Kobner phenomenon by history (KP-h), disease activity, and therapeutic responsiveness in vitiligo vulgaris. DESIGN: Cohort study. SETTING: An outpatient clinic. PATIENTS: Sixty-one consecutive patients with vitiligo vulgaris. INTERVENTION: Three months after a standardized epidermodermal injury was induced, the KP-e was evaluated. For 1 year, UV-B (311 nm) therapy or topical fluticasone propionate plus UV-A therapy was given, depending on the severity of depigmentation. MAIN OUTCOME MEASURES: The presence or absence of the KP-e and the KP-h disease activity as scored on a 6-point scale from -1 to +4 (vitiligo disease activity [VIDA] score) and therapy-induced repigmentation grade. RESULTS: Nineteen (31%) of the patients had a positive KP-h, whereas 37 (61%) showed a positive KP-e (P<.001). The VIDA score did not always predict a positive KP-e, although patients with a positive KP-e had a higher mean VIDA score (VIDA score of 1.6) than did patients with a negative KP-e (VIDA score of 0.5) (P<.001). The responsiveness to UV-B (311 nm) therapy among KP-e-positive or KP-e-negative patients was not significantly different (P=.66). However, KP-e-positive patients who were treated with fluticasone propionate plus UV-A showed a better response than did KP-e-negative patients (P=.01). Among patients responding to both therapies, VIDA scores were significantly decreased (P<.001) compared with VIDA scores before therapy. CONCLUSION: The KP-e may function well as a clinical factor to assess present disease activity and may also predict the responsiveness to fluticasone propionate plus UV-A therapy but not to UV-B (311 nm) therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10206047&dopt=Abstract fluticasone Flonase