Goblet cell rebound and airway dysfunction with corticosteroid withdrawal in a mouse model of asthma.
BACKGROUND
Although corticosteroids are highly effective at preventing allergen-induced increases in goblet cell numbers, we observed in unpublished experiments a rebound increase in goblet cell numbers in mice after the simultaneous withdrawal of corticosteroid and cessation of exposure to allergen that reached levels greater than those observed in mice exposed to allergen alone, without corticosteroid treatment.


OBJECTIVE
To formally explore the goblet cell hyperplasia rebound observed after corticosteroid withdrawal in allergen-exposed mice to determine the mechanism responsible for this previously undescribed pathology.


METHODS
Mice airways were assessed for mucin-containing goblet cells after exposure to varying durations of allergen and corticosteroid.


RESULTS
We confirmed that the simultaneous withdrawal of corticosteroid and cessation of exposure to allergen resulted in a goblet cell hyperplasia rebound that reached levels greater than those observed in allergen-exposed corticosteroid naive mice. Importantly, the goblet cell rebound was associated with a significant airway dysfunction greater than that observed in allergen-exposed corticosteroid naive mice. The goblet cell hyperplasia rebound is independent of the type of corticosteroid or allergen and was associated with an increased level of bronchoalveolar lavage IL-13. Inhibition of IL-13, but not CD4+ T cells, completely inhibited the goblet cell hyperplasia rebound and, critically, the associated airway dysfunction.


CONCLUSIONS
These findings suggest that certain corticosteroid treatment regimes may actually potentiate airway remodeling and dysfunction in patients with asthma and lead to increased exacerbations and worsening of asthma symptoms.
Southam
David S
DS
Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Ellis
Russ
R
Wattie
Jennifer
J
Glass
William
W
Inman
Mark D
MD
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D020397:Goblet Cells / Q000187:drug effects* / Q000473:pathology*; D006965:Hyperplasia / Q000139:chemically induced / Q000503:physiopathology; D018793:Interleukin-13 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012137:Respiratory System / Q000166:cytology / Q000473:pathology
D000305:Adrenal Cortex Hormones; D018793:Interleukin-13