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Journal of leukocyte biology2018; 104(1); 41-48; doi: 10.1002/JLB.3MR1117-436R

Modeling asthma: Pitfalls, promises, and the road ahead.

Abstract: Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource.
©2018 Society for Leukocyte Biology.
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Publication Date: 2018-02-16 PubMed ID: 29451705PubMed Central: PMC6134392DOI: 10.1002/JLB.3MR1117-436RGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the effectiveness and limitations of using different animal models for studying asthma, a recurring inflammatory disease, which affects the lower airways. The article emphasizes the importance of examining diverse experimental models, including mice, guinea pigs, cats, and horses, to research disease induction, airway inflammation, and potential treatments.

Experimental Models for Asthma Research

  • Asthma has been extensively modeled in both wild-type and genetically manipulated mice (Mus musculus). Certain antigen sensitization and disease induction strategies have been successful in reproducing critical features of airway inflammation characteristic of human asthma – notably highlighting the role of type 2 T helper cell cytokines.
  • Most recent disease induction strategies have evolved to include natural aeroallergens with prolonged respiratory challenges without systemic sensitization. Some also integrate tobacco, respiratory viruses, or bacteria as factors to induce exacerbation.

Limitations of Using Mouse Models

  • There are limitations to using mice as models for asthma research. Differences exist in lung size, structure, and physiological responses between mice and humans, which limit to what extent airway dynamics measured in mice would directly parallel human subjects.
  • These differences may make it challenging to apply the outcomes directly to human conditions and may result in failed clinical trials due to the over-reliance on mouse models as predictors of human responses.

Alternative Animal Models

  • The researchers also suggested that other rodent allergic models featuring the guinea pig (Cavia porcellus) might be considered for lung function studies due to their closer resemblance to human respiratory systems.
  • They also highlight the potential of domestic cats (Feline catus) and horses (Equus caballus) as models. Cats and horses develop spontaneous obstructive airway disorders with clinical and pathological features parallel to human asthma. Thus, information gathered from studying these disorders in these animals could be a valuable resource for understanding pathogenesis and treatment of asthma in humans.

The research underscores the need for broader and diversified experimental animal models to better understand asthma pathology and devise efficacious treatments for the heterogeneous disease. It emphasizes the importance of not over-relying on a single model, but rather adopting a comprehensive multi-model approach to advance asthma research.

Cite This Article

APA
Rosenberg HF, Druey KM. (2018). Modeling asthma: Pitfalls, promises, and the road ahead. J Leukoc Biol, 104(1), 41-48. https://doi.org/10.1002/JLB.3MR1117-436R

Publication

Journal of leukocyte biology
ISSN: 1938-3673
NlmUniqueID: 8405628
Country: England
Language: English
Volume: 104
Issue: 1
Pages: 41-48

Researcher Affiliations

Rosenberg, Helene F
  • Inflammation Immunobiology Section and Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Druey, Kirk M
  • Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

MeSH Terms

  • Animals
  • Asthma
  • Disease Models, Animal
  • Humans

Grant Funding

  • Z01 AI000939 / Intramural NIH HHS
  • Z01 AI000939-05 / Intramural NIH HHS
  • Z01 AI000941 / Intramural NIH HHS
  • ZIA AI000941-13 / Intramural NIH HHS

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Citations

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