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Active vaccination against IL-5 bypasses immunological tolerance and ameliorates experimental asthma.

Abstract
Current therapeutic approaches to asthma have had limited impact on the clinical management and resolution of this disorder. By using a novel vaccine strategy targeting the inflammatory cytokine IL-5, we have ameliorated hallmark features of asthma in mouse models. Delivery of a DNA vaccine encoding murine IL-5 modified to contain a promiscuous foreign Th epitope bypasses B cell tolerance to IL-5 and induces neutralizing polyclonal anti-IL-5 Abs. Active vaccination against IL-5 reduces airways inflammation and prevents the development of eosinophilia, both hallmark features of asthma in animal models and humans. The reduced numbers of inflammatory T cells and eosinophils in the lung also result in a marked reduction of Th2 cytokine levels. Th-modified IL-5 DNA vaccination reduces the expression of IL-5 and IL-4 by approximately 50% in the airways of allergen-challenged mice. Most importantly, Th-modified IL-5 DNA vaccination restores normal bronchial hyperresponsiveness to beta-methacholine. Active vaccination against IL-5 reduces key pathological events associated with asthma, such as Th2 cytokine production, airways inflammation, and hyperresponsiveness, and thus represents a novel therapeutic approach for the treatment of asthma and other allergic conditions.
AuthorsM Hertz, S Mahalingam, I Dalum, S Klysner, J Mattes, A Neisig, S Mouritsen, P S Foster, A Gautam
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 167 Issue 7 Pg. 3792-9 (Oct 1 2001) ISSN: 0022-1767 [Print] United States
PMID11564796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Immunoglobulins
  • Interleukin-5
  • Vaccines, DNA
  • Ovalbumin
Topics
  • Animals
  • Asthma (immunology, therapy)
  • B-Lymphocytes (immunology)
  • Bronchial Hyperreactivity (therapy)
  • Cells, Cultured
  • Cytokines (biosynthesis)
  • Immunoglobulins (biosynthesis)
  • Inflammation (therapy)
  • Interleukin-5 (genetics, immunology)
  • Mice
  • Mice, Inbred C3H
  • Ovalbumin (immunology)
  • Pulmonary Eosinophilia (therapy)
  • Self Tolerance
  • Th2 Cells (immunology)
  • Vaccines, DNA (therapeutic use)

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