Limits...
Reduced lung function in a chronic asthma model is associated with prolonged inflammation, but independent of peribronchial fibrosis.

Koerner-Rettberg C, Doths S, Stroet A, Schwarze J - PLoS ONE (2008)

Bottom Line: Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response.In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response.They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-beta1 production in the airways and a Th1 immune response.

View Article: PubMed Central - PubMed

Affiliation: Children's Hospital, Ruhr University of Bochum, Bochum, Germany.

ABSTRACT

Background: In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes.

Methodology/principal findings: Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-beta)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response.

Conclusions: Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-beta1 production in the airways and a Th1 immune response.

Show MeSH

Related in: MedlinePlus

Airway inflammation, goblet cell hyperplasia and airway fibrosis following long and short term OVA challenges.Representative photomicrographs of paraffin-embedded lung sections stained with H&E (left column), Alcian-PAS (middle column) and Masson's trichrome (right column) from short term OVA challenged animals (d–l), long term OVA challenged animals (m–u) and after PBS treatment (a–c) 3 days (row 2 and 5), 4 weeks (row 3 and 6) and 8 weeks (row 4 and 7) after challenges. Magnification: 20-fold for H&E, 20-fold for Masson's trichrome, and 40-fold for Alcian-PAS stained sections.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2215329&req=5

pone-0001575-g002: Airway inflammation, goblet cell hyperplasia and airway fibrosis following long and short term OVA challenges.Representative photomicrographs of paraffin-embedded lung sections stained with H&E (left column), Alcian-PAS (middle column) and Masson's trichrome (right column) from short term OVA challenged animals (d–l), long term OVA challenged animals (m–u) and after PBS treatment (a–c) 3 days (row 2 and 5), 4 weeks (row 3 and 6) and 8 weeks (row 4 and 7) after challenges. Magnification: 20-fold for H&E, 20-fold for Masson's trichrome, and 40-fold for Alcian-PAS stained sections.

Mentions: Both short and long term airway OVA challenges induced marked airway inflammation (Fig 2d, m). Inflammation was more severe after long term than after short term challenges, with respective scores of 3.43±0.14 and 2.68±0.09, p<0.05, n = 6 per group. PBS challenged mice did not develop airway inflammation (average score 0.125±0.06, Fig 2a). All visible airways were affected by inflammation in all OVA challenged animals. Parenchymal inflammation was not detected in any of the groups. Over time, airway inflammation declined, but did not resolve completely by 8 weeks after the final challenge irrespective of the protocol used (Fig 2j, s).


Reduced lung function in a chronic asthma model is associated with prolonged inflammation, but independent of peribronchial fibrosis.

Koerner-Rettberg C, Doths S, Stroet A, Schwarze J - PLoS ONE (2008)

Airway inflammation, goblet cell hyperplasia and airway fibrosis following long and short term OVA challenges.Representative photomicrographs of paraffin-embedded lung sections stained with H&E (left column), Alcian-PAS (middle column) and Masson's trichrome (right column) from short term OVA challenged animals (d–l), long term OVA challenged animals (m–u) and after PBS treatment (a–c) 3 days (row 2 and 5), 4 weeks (row 3 and 6) and 8 weeks (row 4 and 7) after challenges. Magnification: 20-fold for H&E, 20-fold for Masson's trichrome, and 40-fold for Alcian-PAS stained sections.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2215329&req=5

pone-0001575-g002: Airway inflammation, goblet cell hyperplasia and airway fibrosis following long and short term OVA challenges.Representative photomicrographs of paraffin-embedded lung sections stained with H&E (left column), Alcian-PAS (middle column) and Masson's trichrome (right column) from short term OVA challenged animals (d–l), long term OVA challenged animals (m–u) and after PBS treatment (a–c) 3 days (row 2 and 5), 4 weeks (row 3 and 6) and 8 weeks (row 4 and 7) after challenges. Magnification: 20-fold for H&E, 20-fold for Masson's trichrome, and 40-fold for Alcian-PAS stained sections.
Mentions: Both short and long term airway OVA challenges induced marked airway inflammation (Fig 2d, m). Inflammation was more severe after long term than after short term challenges, with respective scores of 3.43±0.14 and 2.68±0.09, p<0.05, n = 6 per group. PBS challenged mice did not develop airway inflammation (average score 0.125±0.06, Fig 2a). All visible airways were affected by inflammation in all OVA challenged animals. Parenchymal inflammation was not detected in any of the groups. Over time, airway inflammation declined, but did not resolve completely by 8 weeks after the final challenge irrespective of the protocol used (Fig 2j, s).

Bottom Line: Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response.In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response.They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-beta1 production in the airways and a Th1 immune response.

View Article: PubMed Central - PubMed

Affiliation: Children's Hospital, Ruhr University of Bochum, Bochum, Germany.

ABSTRACT

Background: In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes.

Methodology/principal findings: Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-beta)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response.

Conclusions: Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-beta1 production in the airways and a Th1 immune response.

Show MeSH
Related in: MedlinePlus