The antiinflammatory activity of budesonide on human airway epithelial cells is lasting after removal of the drug from cultures.
Because of its ability to conjugate extensively with fatty acids within lung cells, it has been suggested that budesonide (Bud) may have a prolonged pharmacologic activity, related to retention of the drug in airway tissues. Using human bronchial epithelial cells (HBECs) as target cells, we evaluated whether Bud could have a long-lasting inhibitory effect on ICAM-1 expression and GM-CSF release. HBECs were cultured in Bud (10 microM) or in medium alone (Ctr) for 24 hr, then extensively washed (to remove Bud) and incubated for an additional 6, 12, or 24 hr with IFN-gamma. ICAM-1 expression and GM-CSF release were then measured by flow cytometric analysis. In Ctr HBECs, IFN-gamma induced a time-dependent upregulation of ICAM-1 expression, significant at 6, 12, or 24 hr (p < 0.05, each comparison), and an increase in GM-CSF release, significant at 24 hr (p < 0.05). The inhibitory effects of Bud preexposure on IFN-gamma-induced ICAM-1 expression and GM-CSF release were then compared with those of a continuous exposure to the drug during IFN-gamma stimulation. Preexposure to Bud (1 and 10 microM) induced a significant inhibition of IFN-gamma-induced ICAM-1 expression (p < 0.05, each comparison), but lower than that observed in HBECs continuously exposed at the same Bud concentrations (p < 0.01, each comparison). In contrast, the inhibition of GM-CSF release was similar in preexposed and in exposed HBECs and statistically significant only at the highest Bud concentration tested (p < 0.05, each comparison). Thus, Bud is effective in vitro in inducing a downregulation lasting 24 hr of mechanisms involved in leukocyte recruitment.
Sabatini
Federica
F
Pulmonary Division, G. Gaslini Institute, Genoa, Italy.
Silvestri
Michela
M
Scarso
Lucia
L
Brazzola
Giancarlo
G
Rossi
Giovanni A
GA
D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D013997:Time Factors
D001993:Bronchodilator Agents; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor