Oncotarget

Research Papers:

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

Huan Wang, Fu-Ling Yan _, Michael Cunningham, Qi-Wen Deng, Lei Zuo, Fang-Lan Xing, Lu-Hang Shi, Shan-Shan Hu and Ya Huang

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Oncotarget. 2016; 7:52404-52415. https://doi.org/10.18632/oncotarget.10497

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Abstract

Huan Wang1, Fu-Ling Yan1, Michael Cunningham3, Qi-Wen Deng1, Lei Zuo1, Fang-Lan Xing1, Lu-Hang Shi2, Shan-Shan Hu2, Ya Huang2

1Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China

2School of Medicine, Southeast University, Nanjing, China

3Public Health School of Southeast University, Nanjing, China

Correspondence to:

Fu-Ling Yan, email: [email protected]

Keywords: stroke, infection, immune, sympathetic pathway, HLA-DR

Received: February 25, 2016    Accepted: June 30, 2016    Published: July 08, 2016

ABSTRACT

Background: Evidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood.

Results: SAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no-infection patients within 48h after stroke onset. NA significantly increased IL-10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing β-arrestin2 expression which reduced the activation of the NF-κB pathway. Propranolol reversed this effect of NA by reducing β-arrestin2 expression.

Materials and Methods: A systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of β-arrestin2, NF-κB, IκBα and phosphor-IκBα were performed to assess the activation of the sympathetic pathway.

Conclusion: IL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration.


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