Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL-5 and peripheral blood eosinophils

Koopmans, Julia; Lutter, René; Jansen, Henk M.; Zee, Jaring S. van der

doi:10.1016/j.jaci.2005.08.016

Cited by 31 publications

(21 citation statements)

References 36 publications

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“…Our results are in agreement with the studies showing that the fluticasone propionate/salmeterol combination reduced the Th2 cytokine synthesis in allergen-stimulated human CD4+ T cells and attenuated serum IL-5 after allergen challenge in persistent asthma [21, 22]. In this study, BUD or BUD/FOR combination reduced the IL-5 and RANTES production in PBMCs even when the drugs were added early (15 min) after the activation of the cells.This result suggests that corticosteroids could downmodulate the progress of the asthmatic inflammatory cascade as long as they are administrated immediately following the activation of immune cells.…”

Section: Discussionsupporting

confidence: 93%

“…Intermittent to mild persistent asthma, pretreatment with fluticasone/salmeterol combination 20 min before allergen exposure did not affect the sputum inflammatory markers after allergen challenge, whereas the serum IL-5 and peripheral blood eosinophils were reduced [22]. Single dose of BUD/FOR combination, administered after allergen inhalation, did not modify the increase in sputum eosinophils and eosinophil cationic protein levels, or exhaled nitric oxide, whereas it attenuated late airway response and airway hyperresponsiveness, and these effects were superior to either BUD or FOR alone [5].…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory Effect of Budesonide Alone and in Combination with Formoterol on IL-5 and RANTES Production from Mononuclear Cells

Soma

Takaku²,

Kobayashi³

et al. 2008

Int Arch Allergy Immunol

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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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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Budesonide Alone and in Combination with Formoterol on IL-5 and RANTES Production from Mononuclear Cells

Soma

Takaku²,

Kobayashi³

et al. 2008

Int Arch Allergy Immunol

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“…Direct evidence for some anti-inflammatory activity of LABAs when added to ICS has also been sought (see Table 1). In each study there was a significant antiinflammatory effect seen with the combination of an inhaled steroid and salmeterol, which was not seen with the same dose of inhaled steroid aloneor in two cases with a considerably higher dose of inhaled steroid alone [20][21][22].…”

Section: Evidence Suggesting An Anti-inflammatory Action Of Labas Whementioning

confidence: 87%

Long-Acting Beta-Agonists in Adult Asthma: Evidence that these Drugs are Safe

Nelson

2006

Primary Care Respiratory Journal

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“…Moreover, improvements in lung function, symptom scores and bronchial hyper-responsiveness following inhaled fluticasone (500 μg daily) in combination with salmeterol (100 μg daily) treatment were associated with changes in sputum α2 macroglobulin and albumin rather than in sputum cell counts [131] and also reduced serum IL-5 and peripheral blood eosinophil numbers [132].…”

Section: Moderate Persistent Asthmamentioning

confidence: 98%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

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International audienceInhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV and the rate of exacerbations. A reduction in the rate of decline in FEV of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases

show abstract

Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL-5 and peripheral blood eosinophils

Cited by 31 publications

References 36 publications

Inhibitory Effect of Budesonide Alone and in Combination with Formoterol on IL-5 and RANTES Production from Mononuclear Cells

Inhibitory Effect of Budesonide Alone and in Combination with Formoterol on IL-5 and RANTES Production from Mononuclear Cells

Long-Acting Beta-Agonists in Adult Asthma: Evidence that these Drugs are Safe

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

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