Abstract
Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.
| Original language | English |
|---|---|
| Pages (from-to) | 165-175 |
| Number of pages | 11 |
| Journal | Immune Network |
| Volume | 16 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2016 |
| Externally published | Yes |
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Keywords
- Airway hyperresponsiveness
- Ambroxol
- Eosinophils
- Neutrophils
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
Immunomodulatory effects of ambroxol on airway hyperresponsiveness and inflammation. / Takeda, Katsuyuki; Miyahara, Nobuaki; Matsubara, Shigeki; Taube, Christian; Kitamura, Kenichi; Hirano, Astushi; Tanimoto, Mitsune; Gelfand, Erwin W.
In: Immune Network, Vol. 16, No. 3, 2016, p. 165-175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunomodulatory effects of ambroxol on airway hyperresponsiveness and inflammation
AU - Takeda, Katsuyuki
AU - Miyahara, Nobuaki
AU - Matsubara, Shigeki
AU - Taube, Christian
AU - Kitamura, Kenichi
AU - Hirano, Astushi
AU - Tanimoto, Mitsune
AU - Gelfand, Erwin W.
PY - 2016
Y1 - 2016
N2 - Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.
AB - Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.
KW - Airway hyperresponsiveness
KW - Ambroxol
KW - Eosinophils
KW - Neutrophils
UR - http://www.scopus.com/inward/record.url?scp=85020118193&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020118193&partnerID=8YFLogxK
U2 - 10.4110/in.2016.16.3.165
DO - 10.4110/in.2016.16.3.165
M3 - Article
VL - 16
SP - 165
EP - 175
JO - Immune Network
JF - Immune Network
SN - 1598-2629
IS - 3
ER -