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Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst

Cellular & Molecular Immunology volume 12, pages 633–644 (2015)Cite this article

Abstract

Influenza A virus (IAV) infection is a major worldwide public health problem. However, the factors involved in mediating the inflammatory response to this infection and their relationships remain poorly understood. Here, we show that IAV infection stimulates the expression of the soluble IL-6 receptor (sIL-6R), a multifunctional protein involved in IL-6 signaling. Interestingly, sIL-6R expression upregulated the levels of its own ligand, IL-6 and those of the pro-inflammatory cytokine IL-32. shRNA-mediated knockdown of sIL-6R suppressed IL-6 and IL-32, indicating that this regulation is dependent on sIL-6R during IAV infection. Furthermore, our results demonstrate that IL-32 participates in a negative feedback loop that inhibits sIL-6R while upregulating IL-6 expression during IAV infection. Therefore, we show that sIL-6R is a critical cellular factor involved in the acute inflammatory response to viral infection.

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Acknowledgements

This work was supported by research grants from the Major State Basic Research Development Program of China (no. 2013CB911102), the National Natural Science Foundation of China (nos. 81271821 and 81461130019) and the National Mega Project on Major Infectious Diseases Prevention (no. 2012ZX10004503-004). The funding agencies had no role in the study design, data collection or analysis, decision to publish or preparation of the manuscript.

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  1. Dr Y Zhu, The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. E-mail: yingzhu@whu.edu.cn

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  1. The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China

    Jun Wang, Qing Wang, Tao Han, Yong-Kui Li, Sheng-Li Zhu, Fang Ao, Jian Feng, Ming-Zhen Jing, Li Wang, Lin-Bai Ye & Ying Zhu

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Wang, J., Wang, Q., Han, T. et al. Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst. Cell Mol Immunol 12, 633–644 (2015). https://doi.org/10.1038/cmi.2014.80

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