Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

Abstract

Background: In asthma T cells are characterized by an increased activation state and by reduced apoptosis. Objective: Because the clinical efficacy of inhaled corticosteroids combined with long-acting b 2 -agonists has been widely demonstrated in asthma, we studied, in vitro, the effect of fluticasone propionate (FP) and salmeterol alone and in combination on the activation and apoptosis of peripheral blood T cells (PBTs), on the expression of phosphorylated nuclear factor kB inhibitor (IkBa), and on the nuclear translocation of glucocorticoid receptor (GR) in PBTs from asthmatic subjects. Methods: Apoptosis was evaluated on the basis of annexin V binding, whereas the expression of caspases 8 and 3 and phosphorylated IkBa, as well as the nuclear translocation of the GR, were evaluated by means of Western blot analysis. Results: FP alone increases and salmeterol alone does not affect T-cell apoptosis. The combination of FP and salmeterol significantly increases PBT apoptosis in comparison with FP alone. FP at the lower concentration, when combined with salmeterol, is equivalent to FP at the higher concentration in inducing PBT apoptosis. The synergy in the induction of cell apoptosis is associated with more efficient activation of caspases 8 and 3. FP plus salmeterol is also able to synergistically reduce the expression of phosphorylated IkBa, thus limiting nuclear factor kB activation. The synergy was related to an increased nuclear translocation of the GR. Conclusion: This study shows that the combination of FP and salmeterol is able to control PBT activation in asthmatic patients more efficiently than FP alone and with a lower concentration of

Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD

“…However, in vitro studies have suggested that there are dose-dependent effects of fluticasone on the inhibition of IL-8 and other mediators released from various types of cells, including airway epithelial cells [24], smooth muscle cells [25] and fibroblasts [26]. A synergistic effect of SFP on the inhibition of mediator release has also been demonstrated [27][28][29][30].…”

Lack of Systemic Side Effects of Long-Term Inhaled Fluticasone Propionate Use in a Cohort of Asthmatic Children

“…Furthermore we did not observe any alteration in bone density and biochemical markers of bone turnover, since another concern is the reduction of bone density that may result from use of high doses of ICS for long-term therapy (17). BMD is usually measured by DEXA since this method is extremely In theframe patients selectedfor the prospective study (n. [9][10][11][12][13][14][15][16][17][18][19]; I Calcium. Phosphorus and Alkaline phosphatase were determined in blood; 2 Calcium clearance was calculated using thefollowingformula: urine calcium/urine creatinine.…”

“…Specific and standardized diagnostic tests for children are not yet available and chronic disease itself might affect growth and bone mineral density (BMD) (13). Moreover, several reports suggest that FP can influence T-cell activation and function ( 14).…”

Advances in asthma pathophysiology: stepping forward from the Maurizio Vignola experience

“…Furthermore, fluticasone propionate was shown to control peripheral blood T-cell activation and induce T-cell apoptosis through activation of caspases 8 and 3 in mild-persistent asthmatics [61]. VIGNOLA et al [62] showed that in mild-persistent asthmatics, low-dose fluticasone propionate was effective in improving symptoms due, at least in part, to the resolution of eosinophilic bronchial inflammation and downregulation of remodelling markers, such as MMP-9 and TIMP-1 levels in induced sputum samples.…”