Open AccessCo‐expression of IL‐18 binding protein and IL‐4 regulates Th1/Th2 cytokine response in murine collagen‐induced arthritis
Author(s) -
Leng Jianhang,
Yao Hangping,
Shen Junya,
Wang Keyi,
Zhuo Guangchao,
Wang Ziwei
Publication year - 2008
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1111/j.1745-7270.2008.00384.x
Subject(s) - microbiology and biotechnology , tumor necrosis factor alpha , interferon gamma , recombinant dna , flow cytometry , interleukin 18 , cytokine , arthritis , splenocyte , endocrinology , alpha (finance) , chemistry , immunology , andrology , medicine , biology , antibody , gene , biochemistry , construct validity , nursing , patient satisfaction
We constructed a recombinant adenoviral vector containing a murine interleukin (IL)‐18 binding protein (mIL‐18BP) and murine IL‐4 (mIL‐4) fusion gene (AdmIL‐18BP/mIL‐4) and used a gene therapy approach to investigate the role of IL‐18BP and IL‐4 in modulating the T‐helper1 and T‐helper2 (Th1/Th2) balance in mice with collagen‐induced arthritis (CIA). Mice with CIA were intra‐articularly injected with 10 7 pfu/6μl of either AdmIL‐18BP/mIL‐4, or a control adenovirus, or with the control vehicle (phosphate‐buffered saline). After intra‐articular gene therapy with AdmIL‐18BP/mIL‐4, the serum levels of tumor necrosis factor‐α (TNF‐α), γ‐interferon (IFN‐γ), IL‐4, IL‐10, and IL‐18 in mice with CIA were assessed by ELISA IFN‐γ‐expressing and IL‐4‐expressing CD4 + T cells from mice splenocytes were monitored by flow cytometry. Mice with CIA at weeks 1, 2, and 4 after intraarticular injection of AdmIL‐18BP/mIL‐4 showed significantly increased serum concentrations of IL‐4 and IL‐10 ( P <0.01 at all time points) but greatly decreased serum concentrations of IFN‐γ, TNF‐α, and IL‐18 ( P <0.01 at all time points) compared to both the control adenovirus and phosphate‐buffered saline control groups. The percentage of IFN‐γ‐producing CD4 + T cells was significantly decreased in response to local AdmIL‐18BP/mIL‐4 treatment. The percentage of IL‐4‐producing CD4 + T cells increased significantly at 1 week after local injection of AdmIL‐18BP/mIL‐4 then returned to normal by week 4. These data indicated the significant modifying effects on the Th1/Th2 imbalance in murine CIA produced by local overexpression of IL‐18BP and IL‐4. Combination treatment with IL‐18BP and IL‐4 is a promising potential therapy for rheumatoid arthritis.