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Cytokine gene therapy of allergic airways inflammation

  • Chapter
Gene Therapy in Inflammatory Diseases

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Although the chain of events leading to asthma is highly complex, the dysregulated production of type 2 cytokines, notably IL-4 and IL-5, by allergen-specific T cells, has emerged as an important causative factor [1, 2]. The symptoms of allergic asthma, including reversible airways occlusion and airways hyperreactivity (AHR), correlate with a local infiltration of the airways mucosa by inflammatory cells, whose recruitment and activation is influenced by IL-3, IL-4, IL-5, granulocyte-macrophage colony stimulating factor and other chemotactic agents produced by activated Th2 cells [3-6]. Indeed, the severity of disease appears to correlate with the degree of airways inflammation and the level of local Th2 cell activity [7, 8]. The molecular and cellular mechanisms underlying the presence of large numbers of Th2 cells in allergic airways remain to be resolved, however their products appear to have profound and specific effects in promoting allergic disease. IL-5, for example, regulates all stages of the development of eosinophils, which are consistently the predominant leukocyte population in the inflammatory infiltrate of asthmatics [5]. IL-4 modulates mast cell activity [4] and, through its influence on Ig class switching, regulates the production of IgE [3] which may specifically sensitize inflammatory cells implicated in allergic airways disease, including mast cells, eosinophils, basophils and macrophages. This leads to the release of inflammatory substances including histamine, leukotrienes, platelet-activating factor, cationic proteins and chemokines which may, in turn, augment the inflammatory process.

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Author information

Authors and Affiliations

  1. Discipline of Immunology and Microbiology, Faculty of Medicine, University of Newcastle, Newcastle, NSW, 2300, Australia

    Alistair J. Ramsay

  2. Divisions of Immunology and Cell Biology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, 0200, Australia

    Yelin Xiong

  3. Divisions of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, 0200, Australia

    Simon P. Hogan & Paul S. Foster

Authors
  1. Alistair J. Ramsay
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  2. Simon P. Hogan
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  4. Yelin Xiong
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Editors and Affiliations

  1. Center for Molecular Orthopaedics, Harvard Medical School, 221 Longwood Avenue, Room BL 152, Boston, MA, 02115, USA

    Christopher H. Evans

  2. University of Pittsburgh School of Medicine, W1246, Biological Sciences Tower, Pittsburgh, PA, 15261, USA

    Paul D. Robbins

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© 2000 Springer Basel AG

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Ramsay, A.J., Hogan, S.P., Foster, P.S., Xiong, Y. (2000). Cytokine gene therapy of allergic airways inflammation. In: Evans, C.H., Robbins, P.D. (eds) Gene Therapy in Inflammatory Diseases. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8478-5_5

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  • DOI: https://doi.org/10.1007/978-3-0348-8478-5_5

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9584-2

  • Online ISBN: 978-3-0348-8478-5

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