Effects of topical glucocorticoids on in vitro lactoferrin glandular secretion: comparison between human upper and lower airways.
BACKGROUND
Mucus hypersecretion is a hallmark of upper and lower airway diseases, such as rhinitis, asthma, and chronic obstructive pulmonary disease. Although topical glucocorticoids are widely used to treat mucosal inflammation, their effect on mucus hypersecretion remains uncertain.


OBJECTIVE
The aim of this study was to investigate the effect of budesonide and beclomethasone dipropionate on in vitro lactoferrin glandular secretion from both human nasal and bronchial mucosa and the potential mediating role of lipocortin 1.


METHODS
Nasal and bronchial explants obtained from patients undergoing surgery were cultured in a controlled atmosphere. Lactoferrin (ELISA) was measured in culture supernatants, and lipocortin 1 (Western blot) was analyzed in explant tissues.


RESULTS
Both budesonide and beclomethasone dipropionate (10(-6) mol/L) decreased spontaneous lactoferrin secretion in nasal and bronchial mucosa. The maximum effect of cortico-steroids (10(-6) mol/L) was obtained at day 3 in bronchial mucosa (budesonide: -56% +/- 9%, P <.05; beclomethasone dipropionate: -32% +/- 6%, P <.05) and at day 5 in nasal mucosa (budesonide: -34% +/- 10%, P <.05; beclomethasone dipropionate: -37% +/- 10%, P <.05). Methacholine (10(-4) mol/L) increased lactoferrin secretion in both bronchial (248% +/- 72%, P <.05) and nasal (107% +/- 28%, P <.05) explants, with this effect being completely abrogated by atropine. Budesonide caused a dose-related inhibitory effect on methacholine-induced lactoferrin secretion that was similar in both bronchial (down to -86% at 10(-6) mol/L) and nasal (down to -73% at 10(-6) mol/L) mucosa. Budesonide (10(-6) mol/L) did not show any effect on lipocortin 1 expression.


CONCLUSIONS
These results suggest that glucocorticoid effects on airway inflammation may include a reduction of mucus hypersecretion in both nasal and bronchial mucosa.
Roca-Ferrer
J
J
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Mullol
J
J
Pérez
M
M
Xaubet
A
A
Molins
L
L
de Haro
J
J
Shelhamer
J
J
Picado
C
C
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D017305:Annexin A1 / Q000096:biosynthesis / Q000502:physiology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001507:Beclomethasone / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D009666:Nose / Q000187:drug effects / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D012636:Secretory Rate / Q000187:drug effects
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019819:Budesonide; D009195:Peroxidase; D007781:Lactoferrin; D001507:Beclomethasone