Circulating level of high mobility group box-1 predicts the severity of community-acquired pneumonia: Regulation of inflammatory responses via the c-Jun N-terminal signaling pathway in macrophages

Abstract

High mobility group box-1 (HMGB-1) has been reported to serve significant roles in various inflammatory diseases. However, the correlation between the circulating level of HMGB-1 and severity of community-acquired pneumonia (CAP) remains unclear. The present study investigated differential alterations in plasma HMGB-1 levels of patients with CAP prior to and following antibiotic treatment, and further analyzed the association between CAP severity and HMGB-1 levels. Furthermore, lipopolysaccharide (LPS)-induced HMGB-1 expression in RAW264.7 macrophages and the relevant signaling pathways were examined. Plasma HMGB-1 levels of 90 patients with CAP and 52 healthy controls were measured using a commercial ELISA. The levels of plasma HMGB-1 were significantly elevated in CAP patients compared with the controls, and antibiotic treatment was effective in reducing HMGB-1 levels. Plasma HMGB-1 correlated with the pneumonia severity index score (r=0.566, P<0.001). Furthermore, LPS-stimulation significantly upregulated HMGB-1 secretion via the c-Jun N-terminal kinase (JNK) signaling pathway in RAW264.7 macrophages, whereas pretreatment with the JNK inhibitor SP600125 markedly downregulated LPS-induced HMGB-1 levels. In conclusion, plasma HMGB-1 levels may serve a role in the diagnosis and clinical assessment of CAP severity. These findings may provide information on novel targets for the treatment of CAP.