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Remission of CVB3‐induced viral myocarditis by in vivo Th2 polarization via hydrodynamics‐based interleukin‐4 gene transfer
Author(s) -
Jiang Zhenggang,
Xu Wei,
Li Kang,
Yue Yan,
Xu Lin,
Ye Fei,
Xiong Sidong
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1215
Subject(s) - myocarditis , immunology , in vivo , tumor necrosis factor alpha , cd8 , immune system , population , biology , cytokine , antibody , medicine , microbiology and biotechnology , environmental health
Background Regulation of Th polarization was critical for the prevention of Coxsackievirus B3 (CVB3) induced myocarditis. In the present study, interleukin (IL)‐4 was over‐expressed by hydrodynamics‐based gene transfection (HGT) to induce the in vivo Th2 bias and evaluate the influence of Th polarization on the pathogenesis of CVB3‐myocaditis. Methods IL‐4 expressing plasmid was delivered into BALB/c mice by HGT after CVB3 infection. In vivo Th polarization was evaluated by detecting expression of Th1/Th2 cytokine, antibody isotype and Th related transcription factor, as well as the proliferation of CD8 + T cells. The severity of myocarditis was assessed by weight loss, serological index of myocarditis, pathological feature, as well as survival rate. Results HGT of IL‐4 plasmid resulted in high‐level and long‐lasting expression of IL‐4 in different organs, which rescued mice from severe heart inflammation and death. This may due to the induction of a Th2‐bised immune response specified with decreased expression of tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ but increased expression of IL‐10 and IL‐4 in serum and heart tissue, more IL‐4 but less IFN‐γ secreting splenic CD4 + T cells, an immunoglobulin G1 isotype switch, increased expression of GATA‐3 and low proliferation of CD8 + T cells, without significant change of virus titer in heart tissue. Conclusions CVB3‐induced myocarditis could be remitted through in vivo Th2 polarization, which has implications for our understanding of the role of Th2 population in immunity to CVB3 infection and for the development of new therapies for CVB3‐myocarditis. Copyright © 2008 John Wiley & Sons, Ltd.