First Author | Hertz M | Year | 2001 |
Journal | J Immunol | Volume | 167 |
Issue | 7 | Pages | 3792-9 |
PubMed ID | 11564796 | Mgi Jnum | J:71618 |
Mgi Id | MGI:2150492 | Doi | 10.4049/jimmunol.167.7.3792 |
Citation | Hertz M, et al. (2001) Active vaccination against il-5 bypasses immunological tolerance and ameliorates experimental asthma. J Immunol 167(7):3792-9 |
abstractText | 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. |