Increased Levels of High Mobility Group Box 1 in the Bronchoalveolar Lavage Fluid of Murine Pneumococcal Pneumonia Model

This study assessed the role of high mobility group box 1 (HMGB1) in pneumococcal pneumonia. Intratracheal challenge of mice with Streptococcus pneumoniae significantly increased HMGB1 levels in bronchoalveolar lavage fluid. Immunostaining of lung sections revealed HMGB1 localization in both alveolar epithelial and infiltrating polymorphonuclear cells in S. pneumoniae-infected mice. In vitro, pneumolysin, a pore-forming pneumococcal toxin, causes HMGB1 release from neutrophils. Additionally, recombinant HMGB1 enhanced TNF-α production in RAW264.7 macrophages, human neutrophils, and THP-1 cells. These findings indicate that neutrophil-derived HMGB1 serves as a pro-inflammatory mediator and exacerbates of lung inflammation during pneumococcal infection.