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29 - Asthma

from PART VI - ANIMAL MODELS OF INFLAMMATION

Published online by Cambridge University Press:  05 April 2014

Bruce D. Levy
Affiliation:
Brigham and Women's Hospital and Harvard Medical School
Charles N. Serhan
Affiliation:
Harvard Medical School
Peter A. Ward
Affiliation:
University of Michigan, Ann Arbor
Derek W. Gilroy
Affiliation:
University College London
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Summary

INTRODUCTION

Asthma is a disease of chronic airway inflammation. This condition is prevalent worldwide and accounts for significant morbidity, excess mortality, and substantial health care expenditures [1, 2]. Asthma is clinically defined by three characteristics, namely reversible airflow obstruction, airway hyperresponsiveness, and airway inflammation [1]. There is no cure for asthma, but many therapies have been developed to lessen the burden of the disease. In light of the need for additional therapeutics to treat and ultimately cure asthma, several animal experimental models have been developed to perform preclinical investigation of asthma pathogenesis and novel therapeutics. Simply stated, asthma is only a human disease. None of the current animal models entirely recapitulates asthma [3], but they have proven very useful in the investigation of asthma traits. In this chapter, the most common animal models of asthma and their features will be described with particular attention to the airway inflammatory responses.

ASTHMA PATHOBIOLOGY

Asthma has a complex pathogenesis and can be considered a clinical syndrome of intermittent dyspnea, wheezing, chest tightness, and/or cough. In most subjects, airway inflammation is present [1]. The inflammatory cell infiltrate is enriched with eosinophils, T lymphocytes and, in some cases, neutrophils, especially in the setting of asthma exacerbations. This complex, chronic airway inflammation is likely initiated and driven by signals from sentinel cells in the airway, including airway epithelia and dendritic cells, responding to provocative stimuli.

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Publisher: Cambridge University Press
Print publication year: 2010

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References

1. Busse, W.W., and Lemanske, R.F. Jr. 2001. Asthma. N Engl J Med 344:350–362.CrossRefGoogle ScholarPubMed
2. Serra-Batlles, J., Plaza, V., Morejon, E., Comella, A., and Brugues, J. 1998. Costs of asthma according to the degree of severity. Eur Respir J 12:1322–1326.CrossRefGoogle ScholarPubMed
3. Wenzel, S., and Holgate, S.T. 2006. The mouse trap: it still yields few answers in asthma. Am J Respir Crit Care Med 174:1173–1176; discussion 1176–1178.CrossRefGoogle ScholarPubMed
4. Zosky, G.R., and Sly, P.D. 2007. Animal models of asthma. Clin Exp Allergy 37:973–988.CrossRefGoogle Scholar
5. Hamelmann, E., Takeda, K., Schwarze, J., Vella, A.T., Irvin, C.G., and Gelfand, E.W. 1999. Development of eosinophilic airway inflammation and airway hyper-responsiveness requires interleukin-5 but not immunoglobulin E or B lymphocytes. Am J Respir Cell Mol Biol 21:480–489.CrossRefGoogle ScholarPubMed
6. Wills-Karp, M., Luyimbazi, J., Xu, X., et al. 1998. Interleukin-13: central mediator of allergic asthma. Science 282:2258–2261.CrossRefGoogle ScholarPubMed
7. Bryan, S.A., O'Connor, B.J., Matti, S., et al. 2000. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356:2149–2153.CrossRefGoogle ScholarPubMed
8. Gavett, S.H., O'Hearn, D.J., Li, X., Huang, S.K., Finkelman, F.D., and Wills-Karp, M. 1995. Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med 182:1527–1536.CrossRefGoogle ScholarPubMed
9. Shapiro, S.D. 2006. Animal models of asthma: pro: allergic avoidance of animal (model[s]) is not an option. Am J Respir Crit Care Med 174:1171–1173.CrossRefGoogle Scholar
10. Drazen, J.M., Takebayashi, T., Long, N.C., De Sanctis., G.T., and Shore, S.A. 1999. Animal models of asthma and chronic bronchitis. Clin Exp Allergy 29(Suppl 2):37–47.Google ScholarPubMed
11. Kips, J.C., Anderson, G.P., Fredberg, J.J., et al. 2003. Murine models of asthma. Eur Respir J 22:374–382.CrossRefGoogle Scholar
12. Abraham, W.M., and Baugh, L.E. 1995. Animal models of asthma. In Asthma and Rhinitis, W.W., Busse and S.T., Holgate (eds), pp. 961–977. Boston: Blackwell Scientific Publications.Google Scholar
13. Finkelman, F.D., and Wills-Karp, M. 2008. Usefulness and optimization of mouse models of allergic airway disease. J Allergy Clin Immunol 121:603–606.CrossRefGoogle ScholarPubMed
14. Irvin, C.G. 2008. Using the mouse to model asthma: the cup is half full and then some. Clin Exp Allergy 38:701–703.CrossRefGoogle Scholar
15. Corry, D.B., and Irvin, C.G. 2006. Promise and pitfalls in animal-based asthma research: building a better mousetrap. Immunol Res 35:279–294.CrossRefGoogle ScholarPubMed
16. Pichavant, M., Goya, S., Hamelmann, E., Gelfand, E.W., and Umetsu, D.T. 2007. Animal models of airway sensitization. Curr Protoc Immunol Chapter 15, Unit 15; 18.Google Scholar
17. Takeda, K., Hamelmann, E., Joetham, A., et al. 1997. Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice. J Exp Med 186:449–454.CrossRefGoogle ScholarPubMed
18. Taube, C., Miyahara, N., Ott, V., et al. 2006. The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. J Immunol 176:3157–3164.CrossRefGoogle Scholar
19. Levy, B.D., De Sanctis, G.T., Devchand, P.R., et al. 2002. Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat Med 8:1018–1023.CrossRefGoogle Scholar
20. Holt, P.G., Batty, J.E., and Turner, K.J. 1981. Inhibition of specific IgE responses in mice by pre-exposure to inhaled antigen. Immunology 42:409–417.Google ScholarPubMed
21. Levy, B.D., Lukacs, N.W., Berlin, A.A., et al. 2007. Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism. FASEB J 21:3877–3884.CrossRefGoogle ScholarPubMed
22. Henderson, W.R. Jr.Tang, L.O., Chu, S.J., et al. 2002. A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model. Am J Respir Crit Care Med 165:108–116.CrossRefGoogle Scholar
23. Serhan, C.N. 2007. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137.CrossRefGoogle ScholarPubMed
24. Haworth, O., Cernadas, M., Yang, R., Serhan, C., and Levy, B. 2008. Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9:873–879.CrossRefGoogle ScholarPubMed
25. Levy, B.D., Kohli, P., Gotlinger, K., et al. 2007. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol 178:496–502.CrossRefGoogle ScholarPubMed
26. Levy, B.D., Bonnans, C., Silverman, E.S., et al. 2005. Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med 172:824–830.CrossRefGoogle ScholarPubMed
27. Sapienza, S., Eidelman, D.H., Renzi, P.M., and Martin, J.G. 1990. Role of leukotriene D4 in the early and late pulmonary responses of rats to allergen challenge. Am Rev Respir Dis 142:353–358.CrossRefGoogle ScholarPubMed
28. Barrett, E.G., Rudolph, K., Bowen, L.E., and Bice, D.E. 2003. Parental allergic status influences the risk of developing allergic sensitization and an asthmatic-like phenotype in canine offspring. Immunology 110:493–500.CrossRefGoogle ScholarPubMed
Busse, W.W., and Lemanske, R.F. Jr. 2001. Asthma. N Engl J Med 344:350–362.CrossRefGoogle ScholarPubMed
Corry, D.B., and Irvin, C.G. 2006. Promise and pitfalls in animal-based asthma research: building a better mousetrap. Immunol Res 35:279–294.CrossRefGoogle ScholarPubMed
Finkelman, F.D., and Wills-Karp, M. 2008. Usefulness and optimization of mouse models of allergic airway disease. J Allergy Clin Immunol 121:603–606.CrossRefGoogle ScholarPubMed
Kips, J.C., Anderson, G.P., Fredberg, J.J., et al. 2003. Murine models of asthma. Eur Respir J 22:374–382.CrossRefGoogle Scholar
Pichavant, M., Goya, S., Hamelmann, E., Gelfand, E.W., and Umetsu, D.T. 2007. Animal models of airway sensitization. Curr Protoc Immunol Chapter 15, Unit 15; 18.Google Scholar
Zosky, G.R., and Sly, P.D. 2007. Animal models of asthma. Clin Exp Allergy 37:973–988.CrossRefGoogle Scholar

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  • Asthma
    • By Bruce D. Levy, Brigham and Women's Hospital and Harvard Medical School
  • Edited by Charles N. Serhan, Peter A. Ward, University of Michigan, Ann Arbor, Derek W. Gilroy, University College London
  • Book: Fundamentals of Inflammation
  • Online publication: 05 April 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139195737.032
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  • Asthma
    • By Bruce D. Levy, Brigham and Women's Hospital and Harvard Medical School
  • Edited by Charles N. Serhan, Peter A. Ward, University of Michigan, Ann Arbor, Derek W. Gilroy, University College London
  • Book: Fundamentals of Inflammation
  • Online publication: 05 April 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139195737.032
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Asthma
    • By Bruce D. Levy, Brigham and Women's Hospital and Harvard Medical School
  • Edited by Charles N. Serhan, Peter A. Ward, University of Michigan, Ann Arbor, Derek W. Gilroy, University College London
  • Book: Fundamentals of Inflammation
  • Online publication: 05 April 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139195737.032
Available formats
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