Co-expression of IL-18 binding protein and IL-4 regulates Th1/Th2 cytokine response in murine collagen-induced arthritis |
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Authors: | Leng Jianhang Yao Hangping Shen Junya Wang Keyi Zhuo Guangchao Wang Ziwei |
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Institution: | Center of Clinical Experimental Medicine, The First People's Hospital of Hangzhou, Hangzhou 310006, China;The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China |
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Abstract: | 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 107pfu/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. |
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Keywords: | interleukin- 18 binding protein interleukin-4 gene therapy rheumatoid arthritis |
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