Flonase
Fluticasone propionate in Crohn's disease.

de Kaski MC, Peters AM, Lavender JP, Hodgson HJ.

Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London.

Fluticasone propionate, a topically active corticosteroid of low systemic bioavailability after oral administration, has been used in a pilot study for the treatment of mild and moderately active Crohn's disease. Twelve patients received oral fluticasone propionate for three weeks, and the effects were monitored using the Crohn's disease activity index and by 111In granulocyte scanning, assessing inflammation from scan appearances, four day faecal excretion of radioactivity, and whole body excretion of radioactivity. All patients completed the trial. No serious side effects were reported. There was a significant fall in Crohn's disease activity index values over the three week treatment period (193 (84) v 122 (51), p less than 0.01). 111In leucocyte scan images were improved (seven patients) or unchanged (five patients). There was a significant fall in excretion of injected radioactivity calculated from whole body data (28 (21)% v 14 (0.7)%, p less than 0.05). There were no changes in plasma cortisol values, either basal or synacthen stimulated. Fluticasone propionate is a promising therapeutic agent for Crohn's disease that offers the possibility of controlling inflammation without inducing systemic corticosteroid side effects and which merits evaluation in a double blind trial versus conventional corticosteroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2060874&dopt=Abstract fluticasone Flonase



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Corticosteroids increase secretory leukocyte protease inhibitor transcript levels in airway epithelial cells.

Abbinante-Nissen JM, Simpson LG, Leikauf GD.

Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056, USA.

Secretory leukocyte protease inhibitor (SLPI) is the predominant antiprotease of the conducting airways and may play a role in reducing airway inflammation. In this study, the effect of corticosteroids used in the treatment of inflammatory airway disease on SLPI transcript levels was investigated. When human airway epithelial cells (9HTEo-) were treated continuously with 10 nM fluticasone propionate, SLPI transcript levels increased within 12 h, with maximal transcript accumulation occurring at 24-48 h. Several corticosteroids (0.1-1,000 nM) were compared, and the following potency in increasing SLPI transcript levels was observed: fluticasone > triamcinolone > or = dexamethasone > methylprednisolone > hydrocortisone. Fluticasone, the most potent corticosteroid, increased SLPI transcript levels at doses as low as 0.1 nM, whereas hydrocortisone, the least potent corticosteroid, was effective at 100 nM. Fluticasone-induced increases in SLPI transcript levels were inhibited by cycloheximide, suggesting protein synthesis may be required for this response. Because proteases are likely to be present when corticosteroids are administered therapeutically, we examined the interaction between elastase and fluticasone and found they act synergistically to increase SLPI transcript levels. Our findings suggest that corticosteroids may exert their antiinflammatory effects in part by increasing airway epithelial cell SLPI production.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7733301&dopt=Abstract fluticasone Flonase



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Fluticasone propionate in the treatment of inflammatory dermatoses.

Chu AC, Munn S.

Unit of Dermatology, Royal Postgraduate Medical School, Hammersmith Hospital, London.

Fluticasone propionate is a new, topically active glucocorticoid which shows high specificity for the glucocorticoid receptor. After topical application systemic absorption is low. The small amount that is absorbed is rapidly and completely inactivated by esterase-catalysed hydrolysis in the liver. Even when applied in large doses under occlusion, there is no evidence of hypothalamic/pituitary/adrenal (HPA) axis suppression. Studies on skin thinning have shown no significant effect on skin thickness after once-daily application of fluticasone propionate 0.05% cream for 8 weeks. This cream has been shown to be highly effective in the treatment of eczema, and once-daily application shows no significant difference in efficacy compared with twice-daily treatment. Limited studies using 0.005% ointment in moderate to severe psoriasis showed similar efficacy to 0.1% betamethasone-17-valerate ointment. Fluticasone propionate 0.05% thus represents a major advance in topical corticosteroids. It has a high safety profile and the cream formulation is effective in a single daily application.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7779663&dopt=Abstract fluticasone Flonase



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Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

Llewellyn-Jones CG, Hill SL, Stockley RA.

Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, UK.

BACKGROUND--Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. METHODS--The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. RESULTS--Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. CONCLUSIONS--These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8202875&dopt=Abstract fluticasone Flonase



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Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion.

Roca-Ferrer J, Mullol J, Lopez E, Xaubet A, Pujols L, Fernandez JC, Picado C.

Fundacio Clinic per a la Recerca Biomedica, Departament de Medicina, Universitat de Barcelona, Catalonia, Spain.

Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may be due to an effect on the release of epithelial cell products responsible for promoting eosinophil survival. We investigated the effect of fluticasone propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on eosinophil survival induced by secretions from cultured nasal epithelial cells. Human epithelial cell-conditioned media (HECM) were generated by cultured epithelial cells obtained from healthy subjects undergoing corrective nasal surgery. Normodense eosinophils isolated from peripheral blood were incubated with HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluticasone propionate had the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 13x10(-8) M), and nedocromil sodium (IC25 >10(-5) M). A significant correlation was found between both inhibitory effects (r=0.955; p<0.05). Topical anti-inflammatory drugs may decrease eosinophil survival by abrogating the promoting effect of epithelial cells. These drugs may exert part of their therapeutic effect by modulating GM-CSF release. The following rank of potency was observed: fluticasone propionate > budesonide > beclomethasone dipropionate > nedocromil sodium. The study of the interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9230235&dopt=Abstract fluticasone Flonase