Basic and clinical immunologySynergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma
Section snippets
Subjects
We selected 15 patients with mild intermittent asthma (age, 9-13 years), according to the criteria of the American Thoracic Society. The diagnosis of asthma and the assessment of its severity were performed at study entry according to Global Initiative for Asthma guidelines.13 None of the patients received any corticosteroid treatment during the previous 2 weeks.
The study fulfilled the criteria of the ethics committee of our hospital, and all subjects, parents, or both provided informed consent.
FP and salmeterol in combination increase apoptosis in resting PBTs
FP significantly increased PBT apoptosis in a dose-dependent manner when compared with baseline values, whereas salmeterol alone did not affect spontaneous PBT apoptosis at either tested time point. Interestingly, the combined presence of FP at all the tested concentrations and salmeterol was able to significantly increase PBT apoptosis at both time points. Moreover, FP at the concentration of 10−9 M when combined with salmeterol was not statistically different from FP at the concentration of 10
Discussion
A main goal of asthma therapy is to achieve optimal control of airway inflammation. ICSs are the mainstay of asthma management and are extremely effective inhibitors of T-cell activation7 and TH2 cytokine production.21
Previous reports demonstrated the clinical utility of combined use of glucocorticoids and LABAs in the improvement of patient symptoms and airflow limitation.10 This study shows, for the first time, a synergistic proapoptotic effect of FP and salmeterol on resting and activated T
References (30)
- et al.
Apoptosis and B-cell lymphoma-2 of peripheral blood T lymphocytes and soluble Fas in patients with allergic asthma
Chest
(2002) Apoptosis: mechanisms of life and death in the immune system
J Allergy Clin Immunol
(1999)- et al.
Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis
J Allergy Clin Immunol
(1999) Death and NF-kappaB in T cell activation: life at the edge
Mol Cell
(2003)- et al.
Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group
Lancet
(1994) - et al.
Ligand-independent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells
J Biol Chem
(1999) - et al.
Salmeterol inhibits the allergen-induced mononuclear cell proliferation and downregulates GM-CSF release and HLA-DR expression by monocytes
Pulm Pharmacol Ther
(1997) - et al.
Salmeterol inhibits interferon-gamma and interleukin-4 production by human peripheral blood mononuclear cells
Int J Immunopharmacol
(1996) - et al.
Effects of salmeterol on secretion of phosphatidylcholine by alveolar type II cells
Life Sci
(2000) - et al.
Protein kinase C regulates FADD recruitment and death-inducing signaling complex formation in Fas/CD95-induced apoptosis
J Biol Chem
(2001)
Effects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects
J Allergy Clin Immunol
Dexamethasone-induced thymocytes apoptosis requires glucocorticoid receptor nuclear translocation but not mitochondrial membrane potential transition
Toxicol Lett
Molecular interactions between glucocorticoids and long-acting beta 2 agonists
J Allergy Clin Immunol
Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids
J Biol Chem
Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action
Biochem Pharmacol
Cited by (0)
Supported by the Italian National Research Council and by GlaxoSmithKline.
Potential conflict of interest: E. Pace has received research support from GlaxoSmithKline. No other conflicts of interest are declared.