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

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.

• Authors: Bingbing Kong, Xiaofeng Wang, Wenping Yang, Xin Zhao, Rong Zhang, Yu Wang
• Journal: Immunologic research (Immunol Res) Vol. 66 Issue 3 Pg. 355-366 (06 2018) ISSN: 1559-0755 [Electronic] United States
• PMID: 29752615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BTLA protein, mouse
• Cytokines
• Immunologic Factors
• Inflammation Mediators
• Receptors, Immunologic
• Simvastatin

Topics

• Animals
• Apoptosis
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cecum (surgery)
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• Humans
• Immunologic Factors (therapeutic use)
• Inflammation Mediators (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Receptors, Immunologic (genetics, metabolism)
• Sepsis (drug therapy)
• Simvastatin (therapeutic use)
• Spleen (pathology)