Proinflammatory cytokines and eosinophil cationic protein on glandular secretion from human nasal mucosa: regulation by corticosteroids.
BACKGROUND
Airway hypersecretion is a common finding in rhinitis and asthma in which proinflammatory cytokines are upregulated. The effect of inflammation on glandular secretion remains unclear.


OBJECTIVE
We sought to investigate the effect of proinflammatory cytokines and eosinophil products in in vitro lactoferrin glandular secretion from human nasal mucosa and the role of corticosteroids and IL-10 in modulating this effect.


METHODS
Nasal explants from patients undergoing turbinectomies were incubated in a controlled atmosphere (50% N(2), 5% CO(2), and 45% O(2)) at 37 degrees C. Nasal explants were incubated with or without IL-1beta, IL-4, IL-5, IL-8, eotaxin, GM-CSF, TNF-alpha, eosinophil cationic protein (ECP), IL-10, and budesonide in a time-course and dose-response fashion. Lactoferrin concentrations in culture supernatants were measured by means of ELISA.


RESULTS
ECP (up to 30%) caused a dose-related stimulation of lactoferrin secretion. TNF-alpha (20 ng/mL) induced a significant increase of lactoferrin release from 8 hours (27.7% +/- 17.8%, P <.05) to 24 hours (40.8% +/- 17.2%, P <.01) compared with that found in media-treated explants. At 24 hours, TNF-alpha caused a dose-related stimulation of lactoferrin secretion (up to 35%). IL-1beta (65.3% +/- 15.2%, P <.05) and GM-CSF (15.7% +/- 6.7%, P <.05), both at 20 ng/mL, exerted a stimulatory effect only at 24 hours, and IL-4, IL-5, IL-8, and eotaxin had no significant effect. Budesonide caused a dose-related inhibition of lactoferrin secretion induced by IL-1beta (down to -76%) and TNF-alpha (down to -70%), whereas IL-10 had no effect.


CONCLUSIONS
ECP and some proinflammatory cytokines (IL-1beta, TNF-alpha, and GM-CSF) may contribute to glandular hypersecretion in the inflamed nose. Corticosteroids may reduce nasal hypersecretion by blocking the direct effect of proinflammatory cytokines on glandular output.
Roca-Ferrer
J
J
Fundació Clínic per a la Recerca Biomèdica, IDIBAPS, Barcelona, Spain.
Mullol
J
J
Xaubet
A
A
Benítez
P
P
Bernal-Sprekelsen
M
M
Shelhamer
J
J
Picado
C
C
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D046508:Culture Techniques; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009195:Peroxidase / Q000096:biosynthesis; D012220:Rhinitis / Q000276:immunology*; D012260:Ribonucleases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase; D012260:Ribonucleases; D007781:Lactoferrin