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Combination Therapy with Thymosin Alpha1 and Dexamethasone Helps Mice Survive Sepsis

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Abstract

Immune dysfunction is a major cause of mortality in septic patients. Current evidence indicates an important role for dendritic cells (DCs) in the pathophysiology of immune dysfunction, and these cells are potential targets of immunomodulation therapies. In the present study, our aim was to enhance the resistance of endotoxemic mice to bacterial translocation and secondary infection and to improve the outcome of these infections using a combination therapy consisting of thymosin alpha1 and dexamethasone in a timely manner according to the changes of DCs’ number. The effect of treatment with dexamethasone (DXM) and thymosin alpha1 (Tα1) on DCs was investigated by examining their number, MHCII and CD86 expression and their capacity to induce T cell activation. Endotoxemic mice were randomly divided into five treatment groups. The survival rates, the levels of TNF-α and IL-10, the occurrence of bacterial translocation, and the ability to clear secondary infections were determined. Additionally, the behavior of DCs over time was also evaluated. Tα1 induced significant increases in DC numbers in vivo, whereas DXM reduced cell numbers both in vitro and in vivo. However, neither drug induced significant changes in the capacity of DCs to induce T cell activation or their expression of MHCII or CD86. Among the five treatment groups, the mice treated with a combination of DXM and Tα1 had the highest survival rate; this increased survival was associated with a decrease in bacterial translocation to extra-intestinal organs and an enhanced ability to eradicate secondary infections by reversing the change in DC numbers during endotoxemia. Immunomodulatory therapy that combines Tα1 and DXM in a timely manner and was based on changes in DCs enhanced the resistance of endotoxemic mice to bacterial translocation and secondary infections, improving the outcome of the infection.

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Conflict of Interest Statement

We declare that we have no financial or personal relationships with other people or organizations that could inappropriately influence our work, and we have no professional or personal interest of any nature in any product, service and/or company that could be construed as influencing the position presented in this manuscript entitled“Combination therapy with thymosin alpha1 and dexamethasone helps mice survive sepsis”.

Grants

This study is supported by the National Basic Research Program (973 Program) in China (no. 2007CB513005 and 2009CB522405) and the Key Project of the National Natural Science Foundation in China (30830098).

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Authors and Affiliations

  1. Research Institute of General Surgery, Jinling Hospital, Nanjng University, No. 305, Eastern Road of Zhongshan, Nanjing, 210002, Jiangsu Province, China

    Xiao-song Xiang, Ning Li, Yun-zhao Zhao, Qiu-rong Li & Jie-shou Li

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  1. Xiao-song Xiang
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  2. Ning Li
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Correspondence to Ning Li.

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Xiang, Xs., Li, N., Zhao, Yz. et al. Combination Therapy with Thymosin Alpha1 and Dexamethasone Helps Mice Survive Sepsis. Inflammation 37, 402–416 (2014). https://doi.org/10.1007/s10753-013-9753-5

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