title: A recombinant DNA plasmid encoding the human interleukin-5 breaks immunological tolerance and inhibits airway inflammation in a murine model of asthma.
abstract: BACKGROUND
  Eosinophils play a pivotal role in the generation of asthma inflammation. Interleukin (IL)-5 is the major activator of eosinophils. We hypothesize that modulating IL-5 activity could be an effective strategy for asthma therapy. In this study, we tested whether the plasmid encoding human IL-5 as a xenogeneic DNA vaccine could induce the production of autoantibodies, and be used for asthma treatment.
  
  
  METHODS
  A eukaryotic plasmid encoding the human IL-5 was constructed, and used as a DNA vaccine. A mouse model of asthma was established to observe its antiasthma activities. Eosinophils in tissue, blood and the bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness (AHR) was determined by whole body plethysmography. Antibody characters and cytokines were detected with immunological methods.
  
  
  RESULTS
  Immunization with a plasmid encoding the human IL-5 as DNA vaccine reduced airway inflammation, reversed Th2 cytokines, and decreased AHR in mice. In addition, this immunization induced the production of polyclonal antibodies that were cross-reactive with native murine IL-5, and IgG1 and IgG2a were the major subclasses. Adoptive transfer of the purified antibodies from the sera of mice immunized with the plasmid encoding the human IL-5 resulted in similar antiasthma effects.
  
  
  CONCLUSIONS
  Our results suggest that active vaccination against IL-5 may be a rational therapeutic approach for the treatment of asthma and potentially other eosinophilic disorders.
authors.affiliation: Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, China. tanhoho@163.com
authors.forename: Guang-Hong
authors.initials: GH
authors.lastname: Tan
authors.forename: Jing-Mei
authors.initials: JM
authors.lastname: Su
authors.forename: Cai-Chun
authors.initials: CC
authors.lastname: Wang
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Yong-Hao
authors.initials: YH
authors.lastname: Huang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Lin
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D019556:COS Cells; D002522:Chlorocebus aethiops; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000276:immunology; D015848:Interleukin-5 / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D004274:DNA, Recombinant; D018836:Inflammation Mediators; D015848:Interleukin-5; D019444:Vaccines, DNA