HMGB1 signaling blocking protects against carbapenem-resistant klebsiella pneumoniae in a murine model of infection

Exp Lung Res. 2018 Aug;44(6):263-271. doi: 10.1080/01902148.2018.1505976. Epub 2018 Dec 29.

Abstract

Purpose of the study: Pulmonary infection with Klebsiella pneumoniae (KP) and carbapenem-resistant Klebsiella pneumoniae (CRKP) significantly contribute to morbidity and mortality in pneumonia. Recent studies have indicated that High-Mobility Group Box 1 Protein (HMGB1) plays an important role in the prevention and treatment of pneumonia. However the role of HMGB1 in CRKP-induced pneumonia has not been addressed. Materials andMethods: In vivo, we successfully established the KP and CRKP-induced pneumonia mouse model. We then tested the anti-HMGB1 IgG prevents CRKP-induced pneumonia.

Results: The mice treated with the anti-HMGB1 IgG ameliorated CRKP-induced pulmonary infiltration of inflammatory cells, dissemination of bacteria and the cytokine storm by suppressing the HMGB1 signaling pathways.

Conclusion: These results indicate that HMGB1 may be an important contributor in these changes of CRKP-induced pneumonia. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CRKP pneumonia.

Keywords: HMGB1; anti-HMGB1 IgG; carbapenem-resistant; pneumonia.

MeSH terms

  • Animals
  • Carbapenems
  • Cytokines / drug effects
  • Drug Resistance
  • HMGB1 Protein / antagonists & inhibitors
  • HMGB1 Protein / immunology
  • HMGB1 Protein / metabolism*
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Inflammation / prevention & control
  • Klebsiella Infections
  • Klebsiella pneumoniae
  • Mice
  • Signal Transduction / drug effects*

Substances

  • Carbapenems
  • Cytokines
  • HMGB1 Protein
  • Immunoglobulin G