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

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.