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. 2002 Jun;11(3):187–190. doi: 10.1080/09622935020138226

In vitro effects of fluticasone propionate on IL-13 production by mitogen-stimulated lymphocytes.

Gabriele Di Lorenzo 1, Maria Luisa Pacor 1, Maria Esposito Pellitteri 1, Sebastiano Gangemi 1, Patrizia Di Blasi 1, Giuseppina Candore 1, Alfredo Colombo 1, Domenico Lio 1, Calogero Caruso 1
PMCID: PMC1781657  PMID: 12137248

Abstract

BACKGROUND: Corticosteroid administration produces multiple immunomodulatory effects, including down-regulation of cytokine production by CD4 T lymphocytes. Fluticasone propionate (FP) (Glaxo Smith&Kline, Greenford, UK), a highly lipophilic topical corticosteroid, has been shown to be safe and effective in the treatment of asthma and of both seasonal and perennial rhinitis. AIMS: To gain insight into the mechanisms of FP therapeutic effects, we evaluated interleukin (IL)-13 (a type 2 cytokine that seemingly plays a pivotal role in allergic mechanisms) production by mitogen-stimulated peripheral blood mononuclear cells (MNC) in vitro, treated or not with FP. METHODS: MNC from 10 healthy subjects and 10 asthmatic atopic patients with Parietaria allergy were stimulated v/v with phytohaemagglutinin (PHA) (50 gamma/ml) or with complete medium alone as a control. Culture supernatants, in vitro treated or not with 10(-7) or 10(-8) M FP, were collected after 48 or 72 h incubation. IL-13 production was assessed by enzyme-linked immunosorbent assay. In random selected samples, after 4 or 24 h of cell cultures, RNA was extracted and IL-4 and IL-5 reverse transcriptase-polymerase chain reaction (RT-PCR) products analyzed. RESULTS: At 48 h, there were no differences in IL-13 concentration in PHA-stimulated cultures between healthy subjects and asthmatic patients (93.6 +/- 18.9 versus 111.0 +/- 25.1 pg/ml). At 72 h, similar results were obtained (63.9 +/- 3.0 versus 73.3 +/- 2.5 pg/ml, respectively). At this time, however, IL-13 concentrations were significantly decreased versus 48 h both in asthmatics (p < 0.001) and in controls (p < 0.001). Treatment with 10(-7) M FP significantly reduced IL-13 production in healthy subjects and asthmatic patients both at 48 h (93.6 +/- 18.9 versus 50.50 +/- 10.6 pg/ml, p < 0.001, and 111.0 +/- 25.1 versus 59.3 +/- 13.6 pg/ml, p < 0.001, respectively) and at 72 h (63.9 +/- 9.6 versus 35.5 +/- 4.4 pg/ml, p < 0.001, and 73.3 +/- 8.0 versus 40.7 +/- 4.5 pg/ml, p < 0.001, respectively). Similar results were obtained with 10(-8) M FP at 48 and 72 h. Accordingly, evaluation of RT-PCR products from selected cell samples showed a FP dosage-dependent inhibition of IL-4 and IL-5 mRNA production both for healthy subjects and asthmatic patients. CONCLUSIONS: FP in vitro impairs IL-13 production by PHA-stimulated MNC from asthmatic and control subjects. This strengthens previous suggestions that IL-13 inhibition by steroids may, at least in part, account for their therapeutic effects.

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Selected References

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  1. Barnes P. J. Molecular mechanisms of corticosteroids in allergic diseases. Allergy. 2001 Oct;56(10):928–936. doi: 10.1034/j.1398-9995.2001.00001.x. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. J., Pedersen S., Busse W. W. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 2):S1–53. doi: 10.1164/ajrccm.157.3.157315. [DOI] [PubMed] [Google Scholar]
  3. Caruso C., Candore G., Modica M. A., Bonanno C. T., Sireci G., Dieli F., Salerno A. Major histocompatibility complex regulation of cytokine production. J Interferon Cytokine Res. 1996 Dec;16(12):983–988. doi: 10.1089/jir.1996.16.983. [DOI] [PubMed] [Google Scholar]
  4. Di Lorenzo G., Esposito Pellitteri M., Drago A., Di Blasi P., Candore G., Balistreri C., Listi F., Caruso C. Effects of in vitro treatment with fluticasone propionate on natural killer and lymphokine-induced killer activity in asthmatic and healthy individuals. Allergy. 2001 Apr;56(4):323–327. doi: 10.1034/j.1398-9995.2001.00879.x. [DOI] [PubMed] [Google Scholar]
  5. Di Lorenzo G., Gervasi F., Drago A., Esposito Pellitteri M., Di Salvo A., Cosentino D., Potestio M., Colombo A., Candore G., Mansueto S. Comparison of the effects of fluticasone propionate, aqueous nasal spray and levocabastine on inflammatory cells in nasal lavage and clinical activity during the pollen season in seasonal rhinitics. Clin Exp Allergy. 1999 Oct;29(10):1367–1377. doi: 10.1046/j.1365-2222.1999.00643.x. [DOI] [PubMed] [Google Scholar]
  6. Di Lorenzo G., Mansueto P., Melluso M., Morici G., Norrito F., Esposito Pellitteri M., Di Salvo A., Colombo A., Candore G., Caruso C. Non-specific airway hyperresponsiveness in mono-sensitive Sicilian patients with allergic rhinitis. Its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season. Clin Exp Allergy. 1997 Sep;27(9):1052–1059. doi: 10.1111/j.1365-2222.1997.tb01257.x. [DOI] [PubMed] [Google Scholar]
  7. Fushimi T., Shimura S., Suzuki S., Saitoh H., Okayama H., Shirato K. Suppression of gene expression and production of interleukin 13 by dexamethasone in human peripheral blood mononuclear cells. Tohoku J Exp Med. 1998 Jun;185(2):157–160. doi: 10.1620/tjem.185.157. [DOI] [PubMed] [Google Scholar]
  8. Ghaffar O., Laberge S., Jacobson M. R., Lowhagen O., Rak S., Durham S. R., Hamid Q. IL-13 mRNA and immunoreactivity in allergen-induced rhinitis: comparison with IL-4 expression and modulation by topical glucocorticoid therapy. Am J Respir Cell Mol Biol. 1997 Jul;17(1):17–24. doi: 10.1165/ajrcmb.17.1.2696. [DOI] [PubMed] [Google Scholar]
  9. Gough N. M. Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Anal Biochem. 1988 Aug 15;173(1):93–95. doi: 10.1016/0003-2697(88)90164-9. [DOI] [PubMed] [Google Scholar]
  10. Hamilos D. L., Thawley S. E., Kramper M. A., Kamil A., Hamid Q. A. Effect of intranasal fluticasone on cellular infiltration, endothelial adhesion molecule expression, and proinflammatory cytokine mRNA in nasal polyp disease. J Allergy Clin Immunol. 1999 Jan;103(1 Pt 1):79–87. doi: 10.1016/s0091-6749(99)70529-4. [DOI] [PubMed] [Google Scholar]
  11. Kleinjan A., Holm A. F., Dijkstra M. D., Boks S. S., Severijnen L., Mulder P. G., Fokkens W. J. Preventive treatment of intranasal fluticasone propionate reduces cytokine mRNA expressing cells before and during a single nasal allergen provocation. Clin Exp Allergy. 2000 Oct;30(10):1476–1485. doi: 10.1046/j.1365-2222.2000.00904.x. [DOI] [PubMed] [Google Scholar]
  12. Kroegel C., Julius P., Matthys H., Virchow J. C., Jr, Luttmann W. Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts. Eur Respir J. 1996 May;9(5):899–904. doi: 10.1183/09031936.96.09050899. [DOI] [PubMed] [Google Scholar]
  13. Lio D., Candore G., Colombo A., Colonna Romano G., Gervasi F., Marino V., Scola L., Caruso C. A genetically determined high setting of TNF-alpha influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity. Hum Immunol. 2001 Jul;62(7):705–713. doi: 10.1016/s0198-8859(01)00264-6. [DOI] [PubMed] [Google Scholar]
  14. Ortolani C., Foresi A., Di Lorenzo G., Bagnato G., Bonifazi F., Crimi N., Emmi L., Prandini M., Senna G. E., Tursi A. A double-blind, placebo-controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis. FLNCO2 Italian Study Group. Allergy. 1999 Nov;54(11):1173–1180. doi: 10.1034/j.1398-9995.1999.00200.x. [DOI] [PubMed] [Google Scholar]
  15. Terada N., Hamano N., Hohki G., Ikeda T., Sai M., Yamashita T., Konno A. The potential role of interleukin-13 in eosinophilic inflammation in nasal mucosa. Allergy. 1998 Jul;53(7):690–697. doi: 10.1111/j.1398-9995.1998.tb03955.x. [DOI] [PubMed] [Google Scholar]

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