Inhibitory Effect of Budesonide Alone and in Combination with Formoterol on IL-5 and RANTES Production from Mononuclear CellsSoma T.a, b · Takaku Y.a · Kobayashi T.a · Hagiwara K.a · Kanazawa M.a · Uematsu K.b · Nagata M.a
aDepartment of Respiratory Medicine, Saitama Medical University and bDivision of Respiratory Medicine, Saitama Medical Center, Saitama, Japan
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Background:The use of a budesonide (BUD)/formoterol (FOR) combination (Symbicort®) for both maintenance and reliever therapy reduces the exacerbation of asthma better than the traditional fixed-dose regimens. In the early stage of exacerbation, the combination therapy could intervene with the development of subsequent airway inflammation. The objective of the study was to evaluate whether in the early stage of cell activation the use of BUD/FOR combination would modify the adhesion of eosinophils or production of cytokines from mononuclear cells. Methods:Human peripheral blood eosinophils, pretreated with BUD (0.1 µM), FOR (0.1 µM) or BUD/FOR combination for 30 min at 37°C, were stimulated with IL-5, leukotriene D4 or phorbol myristate acetate, and eosinophil adhesion was evaluated using an eosinophil peroxidase assay. BUD (0.1 µM), FOR (0.1 µM) or BUD/FOR combination was added to the peripheral blood mononuclear cells stimulated with ionomycin plus phorbol myristate acetate. Concentrations of IL-5 and RANTES in the cell supernatant were measured using ELISA. Results:BUD, FOR or BUD/FOR combination did not modify the eosinophil adhesion induced by any stimulators. In contrast, BUD or BUD/FOR combination significantly reduced the productions of IL-5 and RANTES in peripheral blood mononuclear cells (BUD: p < 0.0001, p = 0.027 vs. control; BUD/FOR: p < 0.0001, p = 0.031 vs. control) when the drugs were added 15 min, but not 4 h, following cell stimulation. Conclusion: In the early stage of exacerbation of asthma, inhaled BUD may suppress the progression of the allergic inflammatory cascade by inhibiting the mononuclear cells. These results also underline the importance of using BUD in rescue inhaler.
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- O’Byrne PM, Bisgaard H, Godard PP, Pistolesi M, Palmqvist M, Zhu Y, Ekström T, Bateman ED: Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med 2005;171:129–136.
- Rabe KF, Atienza T, Magyar P, Larsson P, Jorup C, Lalloo UG: Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomized controlled, double-blind study. Lancet 2006;368:744–753.
- Kuna P, Peters MJ, Manjra AI, Jorup C, Naya IP, Martínez-Jimenez NE, Buhl R: Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract 2007;61:725–773.
Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention. 2006. http://www.ginasthma.com (accessed January 2007).
- Duong M, Gauvreau G, Watson R, Obminski G, Strinich T, Evans M, Howie K, Killian K, O’Byrne PM: The effects of inhaled budesonide and formoterol in combination and alone when given directly after allergen challenge. J Allergy Clin Immunol 2007;119:322–327.
- Barnes PJ: Scientific rationale for using a single inhaler for asthma control. Eur Respir J 2007;29:587–595.
- O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K, Tattersfield A: Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001;164:1392–1397.
- Pauwels RA, Lofdahl C-G, Postma DS, Tattersfield AE, O’Byrne PM, Barnes PJ, Ullman A: Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997;337:1405–1411.
- Johnson M: Development of fluticasone propionate and comparison with other inhaled corticosteroids. J Allergy Clin Immunol 1998;101:S434–S439.
- Kaiser J, Bickel CA, Bochner BS, Schleimer RP: The effects of the potent glucocorticoid budesonide on adhesion of eosinophils to human vascular endothelial cells and on endothelial expression of adhesion molecules. J Pharmacol Exp Ther 1993;267:245–249.
- Liu J, Zhu X, Myo S, Lambertino AT, Xu C, Boetticher E, Munoz NM, Sano M, Cordoba M, Learoyd J, Meliton A, Johnson M, Leff AR: Glucocorticoid-induced surface expression of annexin 1 blocks β2-integrin adhesion of human eosinophils to intercellular adhesion molecule 1 surrogate protein. J Allergy Clin Immunol 2005;115:493–500.
- Leung DY, Martin RJ, Szefler SJ, Sher ER, Ying S, Kay AB, Hamid Q: Dysregulation of interleukin 4, interleukin 5, and interferon γ gene expression in steroid-resistant asthma. J Exp Med 1995;181:33–40.
- Barnes PJ: Corticosteroids: The drugs to beat. Eur J Pharmacol 2006;533:2–14.
Wallin A, Sandström T, Söderberg M, Howarth P, Lundbäck B, Della-Cioppa G, Wilson S, Judd M, Djukanovic R, Holgate S, Lindberg A, Larsson L: The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma. Am J Respir Crit Care Med 1998;158:79–86.
- Persdotter S, Lindahl M, Malm-Erjefalt M, von Wachenfeldt K, Korn SH, Stevens T, Miller-Larsson A: Cooperative inhibitory effects of budesonide and formoterol on eosinophil superoxide production stimulated by bronchial epithelial cell conditioned medium. Int Arch Allergy Immunol 2007;143:201–210.
- Korn SH, Jerre A, Brattsand R: Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells. Eur Respir J 2001;17:1070–1077.
- Profita M, Gagliardo R, Di Giorgi R: Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics. Allergy 2005;60:323–329.
- Pace E, Gagliardo R, Melis M: Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma. J Allergy Clin Immunol 2004;114:1216–1223.
- Spoelstra FM, Postma DS, Hovenga H, Noordhoek JA, Kauffman HF: Additive anti-inflammatory effect of formoterol and budesonide on human lung fibroblasts. Thorax 2002;57:237–241.
Myo S, Zhu X, Myou S: Additive blockade of β2-integrin adhesion of eosinophils by salmeterol and fluticasone propionate Eur Respir J 2004;23:511–517.
- Peek EJ, Richards DF, Faith A: Interleukin-10-secreting ‘regulatory’ T cells induced by glucocorticoids and β2-agonists. Am J Respir Cell Mol Biol 2005;33:105–111.
- Koopmans JG, Lutter R, Jansen HM: Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL-5 and peripheral blood eosinophils. J Allergy Clin Immunol 2005;116:1007–1113.
- Nagata M, Saito K, Tsuchiya K, Sakamoto Y: Leukotriene D4 upregulates eosinophil adhesion via the cysteinyl leukotriene 1 receptor. J Allergy Clin Immunol 2002;109:676–680.
- Kikuchi I, Kikuchi S, Kobayashi T, Hagiwara K, Sakamoto Y, Kanazawa M, Nagata M: Eosinophil trans-basement membrane migration induced by IL-8 and neutrophils. Am J Respir Mol Cell Biol 2006;34:760–765.
- Schleimer RP, Bochner BS: The effect of glucocorticoids on human eosinophils. J Allergy Clin Immunol 1994;94:1202–1213.
- Sutani A, Nagata M, Yamamoto H, Sakurai A, Sakamoto Y: Dexamethasone does not modulate eosinophil adhesion to endothelial cells. Int Arch Allergy Immunol 2001;125 (S1):12–16.
- Kaiser J, Bickel CA, Bochner BS, Schleimer RP: The effects of the potent glucocorticoid budesonide on adhesion of eosinophils to human vascular endothelial cells and endothelial expression of adhesion molecules. J Pharmacol Exp Ther 1993;267:245–249.
- Myo S, Zhu X, Myou S, Meliton AY, Liu J, Boetticher E, Lambertino AT, Xu C, Munoz NM, Leff AR: Additive blockade of β2-integrin adhesion of eosinophils by salmeterol and fluticasone propionate. Eur Respir J 2004;23:511–517.
- Roth M, Johnson PRA, Rudiger JJ, King GG, Ge Q, Burgess JK, Anderson G, Tamm M, Black JL: Interaction between glucocorticoids and 2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling. Lancet 2002;360:1293–1299.
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