Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells.
The effect of formoterol, alone and in combination with budesonide, upon tumour necrosis factor-alpha stimulated (10 ng x mL(-1)) human bronchial epithelial cells was investigated. Addition of formoterol (> or = 10(-10) M) reduced granulocyte macrophage-colony stimulating factor (GM-CSF) levels, as assessed by enzyme-linked immunosorbent assay, by 40-50% and increased interleukin (IL)-8 levels by approximately 50%. The effects of formoterol were long lasting (23 h). Budesonide (10(-8) M) reduced the amounts of both cytokines (GM-CSF and IL-8) by 40%. Simultaneous addition of formoterol and budesonide reduced GM-CSF levels approximately 75%, while IL-8 levels were decreased approximately 40%, similar to the reduction obtained with budesonide alone. The glucocorticoid receptor (GR) antagonist RU486 did not influence the effect of formoterol, suggesting no involvement of the GR. Formoterol rapidly induced an elevation in intracellular cyclic adenosine monophosphate, which was reduced in the presence of propranolol. In addition, the alterations in cytokine secretion induced by formoterol could be fully blocked by propranolol, demonstrating that these effects are beta2-receptor mediated. In conclusion, the combination of budesonide and formoterol reduces the secretion of granulocyte macrophage-colony stimulating factor to basal levels and counteracts the capacity of formoterol alone to induce interleukin-8 production, modulations which may facilitate improved asthma control.
Korn
S H
SH
Inflammatory Pharmacology, Astra-Zeneca, Lund, Sweden.
Jerre
A
A
Brattsand
R
R
D001249:Asthma / Q000276:immunology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D004983:Ethanolamines; D016209:Interleukin-8; D016211:Transforming Growth Factor alpha; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011433:Propranolol; D000242:Cyclic AMP; D000068759:Formoterol Fumarate