Respiratory Models
Pharmacology & Efficacy Studies for Lung Inflammation & Asthma
Lung Inflammation is a critical component of many lung diseases including asthma. Asthma is classified as a chronic inflammatory disease of the airways, however the underlying physiology and immunological pathways are not completely understood. Allergan challenge models are commonly used to study mechanisms involved in lung inflammation and allergic asthma. Ovalbumin-induced allergic asthma is a widely used model to reproduce the airway eosinophilia, pulmonary inflammation and elevated IgE levels found during asthma.
MLM Medical Labs offers models to study the inflammatory components involved in lung inflammation and asthma.
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Lung Injury Models
LPS-Induced Lung Inflammation/Acute Lung Injury (ALI) Screen
Species Available: Mouse LPS Lung, Rat LPS Lung
LPS lung inflammation models are widely used to study host-response patterns in the pulmonary compartment. The LPS lung inflammation model is an acute lung inflammation model where researchers can observe the pulmonary response following exposure to bacteria. Following induction by the intranasal administration of LPS, leukocytes (mainly neutrophils) are recruited to the lung within 4 hours. Using this model, it is possible to measure and characterize the cellular profile of recruited leukocytes to the lung airways as well as the levels of pro-inflammatory cytokines.
Available Assessments
- Cell populations in the BALF by FACS
- Cytokine profile in BALF or lung tissue by multiplex assay
- WBC
- Total Protein
Biomarker Data in Mouse Model
Asthma Models
Ovalbumin (OVA) induced Allergic Asthma Efficacy Model
Commonly Utilized Model of Airway Inflammation
Species available: Mouse Acute Model, Mouse Chronic Model
The immune response during asthma is well preserved between mice and humans. In human asthma, eosinophils and lymphocytes are found to infiltrate the bronchial mucosa. Increased mucus secretion and production of Th2 associated cytokines such as IL-4, IL-5 and IL-13 are also found. IL-4 induces differentiation of CD4 T cells into Th2 cells, induces the proliferation of activated B cells and is the major cytokine involved in B cell class switching to IgE (the antibody isotype most associated with human asthma). IL-5 is involved in eosinophil activation and also facilitates B cell growth and antibody production. The activities of IL-13 and IL-4 show a high level of overlap, although it is thought that IL-4 acts primarily in the initial sensitization, with IL-13 more important during secondary exposure to the allergen. In addition to inducing IgE production, IL-13 can induce AHR, goblet cell metaplasia and air- way glycoprotein hyper-secretion, which all contribute to airway obstruction. Mast cells are also central to the development of asthma due to their ability to release an array of preformed and newly synthesized inflammatory mediators such as cytokines, leukotrienes and prostaglandins.
While we know many factors and events that play an important role in the initiation, progression and persistence of allergic asthma, there is still a lot to be understood about the immuno-regulatory mechanisms. The murine OVA-induced asthma model is a widely used model that results in the characteristic features of asthma allowing the study and assessment of novel treatments.
Assessments:
- Cell populations in the BALF by FACS
- Cytokine profile in BALF or lung tissue by multiplex
- IgE levels
- Total Protein
- Histology
Cytokine Profile in the OVA-induced Asthma Model
House Dust Mite (HDM) induced Asthma
Allergic Asthma Model with High Translational Value
The House Dust Mite (HDM) murine model of allergic asthma is used to assess therapies with potential indications in airway inflammation and/or pulmonary inflammation driven primarily by repeated exposure to allergens. As roughly 85% of allergic asthma sufferers have increased HDM-specific serum IgE levels, the HDM model demonstrates significant relevance for investigating the molecular mechanisms of allergic asthma pathogenesis.
HDM-induced asthma recapitulates many of the features of human allergic asthma, including a primarily Th2- associated cytokine response, eosinophilic infiltration into the lungs, airway hyper responsiveness (AHR) and epithelial tissue remodeling. The model consists of a subcutaneous HDM sensitization followed by intranasal challenge of HDM. Main readouts include broncheoalveolar lavage fluid (BALF) cellularity assessment and cytokine production, with optional blood and lung tissue collection for further downstream analysis.
Assessments:
- Cell populations in the BALF by FACS
- Cytokine profile in the BALF or lung tissue homogenate by multiplex
- IgE levels
- Total Protein
- Histology