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  • Title: Neutralization of interleukin-10 or transforming growth factor-β decreases the percentages of CD4+ CD25+ Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival.
    Author: Hiraki S, Ono S, Tsujimoto H, Kinoshita M, Takahata R, Miyazaki H, Saitoh D, Hase K.
    Journal: Surgery; 2012 Feb; 151(2):313-22. PubMed ID: 21982068.
    Abstract:
    OBJECTIVES: To investigate the role of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) in septic conditions, and to examine the potential of targeting them for the treatment of sepsis. BACKGROUND: Sepsis-induced immunosuppression has long been considered a factor in late mortality of patients with sepsis. Although Tregs are central to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the late stages of sepsis. METHODS: Peripheral blood mononuclear cells (MNCs) in septic patients and liver or spleen MNCs collected after a cecal ligation and puncture (CLP) model in C57BL/6 mice were examined to evaluate the roles of Tregs and the correlation of transforming growth factor (TGF)-β or interleukin (IL)-10 with their activity. We next examined the effects of neutralization of TGF-β or IL-10 on the percentages of Tregs in CD4+ T cells and the survival rates of septic mice. RESULTS: The percentages of Tregs in peripheral blood lymphocytes were significantly increased in patients with sepsis, and there was a significantly positive correlation between serum IL-10 levels and the percentage of Tregs. CLP injury increases the percentages of Tregs in the CD4+ T cells in the spleen, and there was a significantly positive correlation between the percentages of Tregs and the serum IL-10 or TGF-β levels. The neutralization of TGF-β or IL-10 decreased the percentages of Tregs in CD4+ T cells, restored the percentages of CD4+ T cells in spleen MNCs, and improved survival rates in septic mice. CONCLUSION: We found an increase in the percentages of Tregs in peripheral blood circulating CD4+ T cells from patients with sepsis, and in splenic MNCs from septic mice, and observed that regulation of Tregs by neutralizing IL-10 or TGF-β might represent a novel strategy for treating the immunosuppressive conditions in sepsis.
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