Additive anti-inflammatory effect of formoterol and budesonide on human lung fibroblasts

Abstract

Background: It has been shown that treatment with a long acting β 2 agonist in addition to a glucocorticoid is beneficial in the treatment of asthma. In asthma inflammatory cells, particularly eosinophils, migrate into the pulmonary tissue and airway lumen by means of adhesion molecules expressed on resident tissue cells-that is, fibroblasts-and become activated by cytokines and adhesive interactions. A study was undertaken to determine whether an interaction exists between the long acting β 2 agonist formoterol and the glucocorticoid budesonide on inhibition of adhesion molecule expression, as well as chemo/cytokine production by human lung fibroblasts. Methods: Lung fibroblasts were preincubated with therapeutically relevant drug concentrations of 10 -8 M to 10 -10 M. Cells were stimulated with interleukin (IL)-1β (1 or 10 U/ml) for 8 hours and supernatants were collected for measurement of GM-CSF and IL-8 concentrations. The cells were fixed and subjected to a cell surface ELISA technique to measure the expression of ICAM-1 and VCAM-1. Results: Formoterol exerted an additive effect on the inhibition of IL-1β stimulated ICAM-1 and VCAM-1 upregulation and GM-CSF production by budesonide in concentrations of 10 -9 M and above (p<0.05). IL-8 production was not influenced by formoterol. Conclusion: Formoterol exerts an additive effect on the anti-inflammatory properties of budesonide. In vitro data support the finding that the combination of budesonide and formoterol in asthma treatment strengthens the beneficial effect of either drug alone.

Opposite effect of corticosteroids and long‐acting β2‐agonists on serum‐ and TGF‐β1‐induced extracellular matrix deposition by primary human lung fibroblasts

“…In agreement with their anti-inflammatory properties (Frieri, 1999), corticosteroids significantly downregulated the spontaneous and FCS-induced release of both cytokines. However, the effect of LABA on pro-inflammatory mediators is controversially discussed and may depend on the cell type and stimulus (Spoelstra et al, 2002;Reid et al, 2003;Baouz et al, 2005). Here, LABA alone did not affect IL-6 and IL-8 secretion by fibroblasts, and in combination, LABA did not further modulate the decrease of the corticosteroids under both serum-free and 5% FCS conditions.…”

Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease

“…In view of these effects, and since complementary actions of b 2 -agonists and corticosteroids have been shown both in vitro [20,21] and in patients with asthma [22,23], this study was designed to evaluate the efficacy and safety of budesonide/formoterol in a single inhaler (Symbicort1; AstraZeneca, Lund, Sweden) against placebo and both monocomponents in patients with moderate-to-severe COPD.…”

Proliferation is not increased in airway myofibroblasts isolated from asthmatics

“…Interleukin (IL)-1 can elicit the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) [13,14] and IL-8 [15] from myofibroblasts and airway smooth muscle. These cytokines play important roles in promoting recruitment, maturation and survival of eosinophils, mast cells and neutrophils, while GM-CSF may also contribute to subepithelial fibrosis by regulating collagen deposition [16].…”