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

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.