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IL-33 Treatment Attenuates the Systemic Inflammation Reaction in Acinetobacter baumannii Pneumonia by Suppressing TLR4/NF-κB Signaling

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Abstract

Interleukin (IL)-33 treatment has been reported to reduce mortality in a rat model of sepsis, and the present study aimed to determine whether this effect of IL-33 is achieved through a reduction in the systemic inflammatory response in Acinetobacter baumannii pneumonia. After induction of pneumonia, rats were treated with normal saline or IL-33, and mortality over 5 days was recorded. Inflammation within lung tissues was evaluated by hematoxylin and eosin staining as well as measurement of the concentrations of IL-8 and tumor necrosis factor alpha (TNF-α) in the bronchoalveolar lavage fluid (BALF) and plasma by enzyme-linked immunosorbent assay. In addition, the expression of Toll-like receptor 4 (TLR4), ST2, and nuclear factor kappa B (NF-κB) in rat lung tissues was assessed by western blotting. The result showed that the mortality rate and systemic inflammation were significantly increased in rats upon infection with A. baumannii, as evidenced by significant increases in the IL-8 and TNF-α levels in BALF and plasma as well as increased NF-κB activity and TLR4 expression in rat lung tissues. Importantly, IL-33 (1 μg/kg) treatment significantly decreased mortality and pulmonary inflammation in A. baumannii-infected rats. Moreover, IL-33 treatment suppressed the elevation of IL-8 and TNF-α levels and inhibited TLR4 expression and NF-κB activation. Overall, these results suggest that IL-33 may decrease the mortality and inhibit the systematic inflammatory response associated with A. baumannii pneumonia by suppressing TLR4/NF-κB signaling.

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Funding

This study was supported by the Chinese National Nature & Science Foundation (Grant Number 81360241) and the Guizhou Province 2012 Project (Grant Number [2012]2238).

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Authors and Affiliations

  1. Department of Respiratory Medicine, Guizhou Provincial People’s Hospital, 83 Zhongshan Road, Nanming District, Guiyang, 550002, China

    Chunhong Peng, Jin Han, Xianwei Ye & Xiangyan Zhang

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  1. Chunhong Peng and Jin Han contributed equally to this work.

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    1. Chunhong Peng
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    Correspondence to Chunhong Peng.

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    Peng, C., Han, J., Ye, X. et al. IL-33 Treatment Attenuates the Systemic Inflammation Reaction in Acinetobacter baumannii Pneumonia by Suppressing TLR4/NF-κB Signaling. Inflammation 41, 870–877 (2018). https://doi.org/10.1007/s10753-018-0741-7

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