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.
Subject(s)
Animals , Mice , Ambroxol , Asthma , Bronchoalveolar Lavage , Cytokines , Eosinophilia , Eosinophils , Goblet Cells , In Vitro Techniques , Inflammation , Interleukin-10 , Interleukin-12 , Interleukin-13 , Interleukin-4 , Interleukin-5 , Lung , Macrophages, Alveolar , Metaplasia , Models, Theoretical , Mucociliary Clearance , Neutrophils , Ovalbumin , Ovum , Oxidative Stress , Pulmonary Disease, Chronic Obstructive , Up-RegulationABSTRACT
Asthma is a complex syndrome with many clinical phenotypes in children and adults. Despite the rapidly increasing prevalence, clinical investigation and epidemiological studies of asthma, the successful introduction of new drugs has been limited due to the different disease phenotypes and ethical issues. Mouse models of asthma replicate many of the features of human asthma, including airway hyperreactivity, and airway inflammation. Therefore, examination of disease mechanisms in mice has been used to elucidate asthma pathology and to identify and evaluate new therapeutic agents. In this article, we discuss the various animal models of asthma with a focus on mouse strains, allergens, protocols, and outcome measurements.
Subject(s)
Adult , Animals , Child , Humans , Mice , Allergens , Asthma , Inflammation , Models, Animal , Phenotype , PrevalenceABSTRACT
Asthma is a complex syndrome with many clinical phenotypes in children and adults. Despite the rapidly increasing prevalence, clinical investigation and epidemiological studies of asthma, the successful introduction of new drugs has been limited due to the different disease phenotypes and ethical issues. Mouse models of asthma replicate many of the features of human asthma, including airway hyperreactivity, and airway inflammation. Therefore, examination of disease mechanisms in mice has been used to elucidate asthma pathology and to identify and evaluate new therapeutic agents. In this article, we discuss the various animal models of asthma with a focus on mouse strains, allergens, protocols, and outcome measurements.