A recombinant DNA plasmid encoding the human interleukin-5 breaks immunological tolerance and inhibits airway inflammation in a murine model of asthma.
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.
Tan
Guang-Hong
GH
Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, China. tanhoho@163.com
Su
Jing-Mei
JM
Wang
Cai-Chun
CC
Huang
Feng-Ying
FY
Wang
Hua
H
Huang
Yong-Hao
YH
Lin
Ying-Ying
YY
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
D004274:DNA, Recombinant; D018836:Inflammation Mediators; D015848:Interleukin-5; D019444:Vaccines, DNA