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Effects of simvastatin on the function of splenic CD4+ and CD8+ T cells in sepsis mice

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Abstract

Simvastatin may be beneficial for treating sepsis due to its immune-regulating properties, although the mechanisms remain elusive. Herein, we hypothesized simvastatin may attenuate T cell dysfunction induced by sepsis. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pre-treated with simvastatin (0.2 μg/g of body weight) before CLP. The expression of B and T lymphocyte attenuator (BTLA) on splenic CD4+ T cells and T cell apoptosis, CD4+ and CD8+ T cells were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of TNF-α and interleukin 10 (IL-10) in the spleen and plasma levels of presepsin, IL-1β, and IL-6 were determined using enzyme-linked immunosorbent assay. Simvastatin markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. Simvastatin-treated mice had significantly decreased the percentages of negative costimulatory receptor BTLA on CD4 T cell expression. Simvastatin markedly reduced T cell apoptosis through downregulating the Fas/FasL expression and decrease the percentage of caspase-3 activity in spleen tissue. There was significantly less depletion of splenic CD4+ and CD8+ T cells in simvastatin-treated mice. Simvastatin reduced plasma levels of presepsin, IL-1β, and IL-6. Simvastatin can be a powerful regulator of immune function under sepsis conditions by improving T cell function in sepsis.

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Acknowledgments

We thank all the people who helped us to carry out this work.

Funding

This work was funded in part by Shenyang Science and Technology Project of China (Grant No.17-203-958).

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Authors and Affiliations

  1. Emergency Department, Shengjing Hospital Affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China

    Bingbing Kong, Xiaofeng Wang, Wenping Yang, Xin Zhao, Rong Zhang & Yu Wang

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  1. Bingbing Kong
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  2. Xiaofeng Wang
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  3. Wenping Yang
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  4. Xin Zhao
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  5. Rong Zhang
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Correspondence to Yu Wang.

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Kong, B., Wang, X., Yang, W. et al. Effects of simvastatin on the function of splenic CD4+ and CD8+ T cells in sepsis mice. Immunol Res 66, 355–366 (2018). https://doi.org/10.1007/s12026-018-8994-7

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