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Neutralization of interleukin-1 beta attenuates silica-induced lung inflammation and fibrosis in C57BL/6 mice

  • Organ Toxicity and Mechanisms
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Abstract

The inflammation and fibrosis induced by silica dust are considered to be substantial responses in silicosis progression. Interleukin-1 beta (IL-1β) plays an important role in silica-induced lung inflammation, but the mechanisms that underlie the influence of IL-1β on the progression of silicosis remain unclear. In this study, the role of IL-1β in silica-induced inflammation and fibrosis was evaluated by administering a suspension of 2.5-mg silica dust, either with or without 40 μg anti-mouse IL-1β monoclonal antibody (mAb), to the lungs of male C57BL/6 mice. Silica + anti-IL-1β mAb-treated mice showed the depletion of IL-1β as well as the attenuation of inflammation, as evaluated in the bronchoalveolar lavage fluid (BALF) and histological sections from 1 to 84 days after silica exposure. Further study of the BALF indicated that inhibition of IL-1β could reduce the contents of tumor necrosis factor-alpha and monocyte chemoattractant protein-1. The real-time PCR and pathology results showed that the neutralization of IL-1β attenuated silica-induced fibrosis by inhibiting the gene expression of transforming growth factor-beta 1, collagen I and fibronectin. The examination of Th1-cytokine and Th2-cytokine suggested that depletion of IL-1β decelerated the Th1/Th2 balance toward a Th2-dominant response. In conclusion, the present study suggests that the neutralization of IL-1β attenuates silica-induced inflammation and fibrosis by inhibiting other inflammatory and fibrogenic mediators and modulating the Th1/Th2 balance.

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Acknowledgments

This work was financially supported by grants from National Basic Research Program of China (2011CB503804, 2011CB512102) and the National Natural Science Foundation of China (30972451).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Occupational and Environmental Health and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Jiali Guo, Nali Gu, Yun Zhou, Yi Rong, Ting Zhou, Xiuqing Cui & Weihong Chen

  2. Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, 110001, Liaoning, China

    Jie Chen

  3. Institute of Health Surveillance, Analysis and Protection, Hubei Center for Disease Control and Prevention, Wuhan, 430070, Hubei, China

    Tingming Shi & Wenxiang Yang

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  1. Jiali Guo
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  2. Nali Gu
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  10. Weihong Chen
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Correspondence to Weihong Chen.

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Guo, J., Gu, N., Chen, J. et al. Neutralization of interleukin-1 beta attenuates silica-induced lung inflammation and fibrosis in C57BL/6 mice. Arch Toxicol 87, 1963–1973 (2013). https://doi.org/10.1007/s00204-013-1063-z

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  • DOI: https://doi.org/10.1007/s00204-013-1063-z

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