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Nemonoxacin Has Immunoprotective Effects on Reducing Mortality in Lipopolysaccharide-Induced Mouse Sepsis Model

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Abstract

Nemonoxacin is a novel non-fluorinated quinolone. The effect of nemonoxacin on modulation of host immune response is not known. We sought to determine whether nemonoxacin has immunoprotective effects on lipopolysaccharide (LPS)-induced mouse sepsis model. Therefore, mice were challenged with lethal dose LPS (12.5 mg/kg) only or LPS with multi-dose nemonoxacin (40 mg/kg q12h) by intraperitoneal injection, and the results showed nemonoxacin could significantly reduce mortality from 80 to 30% in this model. The effect of nemonoxacin on immune cells in vivo and in vitro was also investigated. Mice were treated with sublethal LPS (5 mg/kg) or LPS + nemonoxacin, the myeloid cell subsets in mouse spleen were analyzed by flow cytometry, and cytokines in mouse serum were measured by ELISA. Additionally, mouse macrophage RAW264.7 cells were treated with LPS or LPS + nemonoxacin to investigate the immune modulatory effect of nemonoxacin in vitro, and the level of cytokines in cell culture supernatant was determined by ELISA. Analysis of myeloid cell subsets in the spleen showed nemonoxacin pretreatment could significantly inhibit LPS-induced proliferation of macrophages and dendritic cells but have no effect on neutrophils. Nemonoxacin could significantly reduce the expression of pro-inflammatory cytokines IL-6 and TNF-α while increase anti-inflammatory cytokine IL-10 expression, which were induced by LPS in vivo and in vitro. Finally, the immunomodulation of nemonoxacin in macrophage phagocytosis was also examined. The results displayed nemonoxacin pretreatment could significantly enhance the phagocytic function of macrophage. In conclusion, nemonoxacin has immune modulatory and protective effect on LPS-induced inflammation in vivo and in vitro.

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Abbreviations

LPS:

lipopolysaccharide

ELISA:

enzyme-linked immunosorbent assay

IL-1:

interleukin-1

IL-6:

interleukin-6

IL-10:

interleukin-10

TNF-α:

tumor necrosis factor alpha

i.p.:

intraperitoneal injection

RAW264.7:

macrophage; Abelson murine leukemia virus transformed

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Acknowledgments

We would like to thank Zhenda Shi, a Post-Doctor from Georgia State University, Atlanta, GA, USA, for his valuable help in animal model construction.

Funding

This study was financially supported by the Major Research and Development Project of Innovative Drugs, Ministry of Science and Technology of China (2017ZX09304005) and the Shanghai Natural Science Fund (No. 17ZR1425100).

Author information

Author notes

  1. Nanye Chen and Xin Li contributed equally to this work.

Authors and Affiliations

  1. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China

    Nanye Chen, Xin Li, Beining Guo, Dongfang Lin & Xu Zhao

  2. Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China

    Nanye Chen

  3. Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China

    Xin Li, Beining Guo, Dongfang Lin & Xu Zhao

  4. Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA

    Jun Zou

  5. Minhang Hospital, Fudan University, Shanghai, China

    Xiang Li

  6. The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China

    Jinwei Huang

  7. Minhang Hospital & School of Pharmacy, Department of Biological Medicines Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China

    Meiqing Feng

Authors
  1. Nanye Chen
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  2. Xin Li
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  3. Beining Guo
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  9. Xu Zhao
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Corresponding authors

Correspondence to Meiqing Feng or Xu Zhao.

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The authors declare that they have no conflict of interest.

Ethical Approval

The experimental protocol was approved by the Animal Research Committee of School of pharmacy, Fudan University, Shanghai, China. (No. 2019-03-HSYY-ZX-01) The care and handling of the animals were carried out according to the institutional and national guidelines.

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Chen, N., Li, X., Guo, B. et al. Nemonoxacin Has Immunoprotective Effects on Reducing Mortality in Lipopolysaccharide-Induced Mouse Sepsis Model. Inflammation 43, 2276–2286 (2020). https://doi.org/10.1007/s10753-020-01296-9

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  • DOI: https://doi.org/10.1007/s10753-020-01296-9

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