Additive anti-inflammatory effect of formoterol and budesonide on human lung fibroblasts.
BACKGROUND
It has been shown that treatment with a long acting beta2 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 beta2 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)-1beta (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-1beta 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.


CONCLUSIONS
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.
Spoelstra
F M
FM
Department of Allergology, University Hospital Groningen, Groningen, The Netherlands.
Postma
D S
DS
Hovenga
H
H
Noordhoek
J A
JA
Kauffman
H F
HF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects*; D000068759:Formoterol Fumarate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004983:Ethanolamines; D007375:Interleukin-1; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068759:Formoterol Fumarate