HMGB1 and metabolic pathways in Acinetobacter baumannii pneumonia: an associative study.

BACKGROUND: Acinetobacter baumannii (AB) pneumonia often leads to lung injury and multisystem dysfunction. High Mobility Group Box 1 (HMGB1) is known to play a crucial role in the progression of AB. In this study, we aimed to investigate the association between HMGB1 levels and the severity of AB pneumonia. METHODS: We conducted a study with a total of 91 participants, divided into three groups: patients with AB infection (n = 44), patients with AB complicated multiple organ disfunctions (MODs) (n = 19), and healthy controls (n = 28). Clinical parameters were assessed, HMGB1 levels were measured, and metabolomic analysis was performed. Validation experiments were conducted using SD rats. RESULTS: Patients with AB exhibited significantly elevated levels of HMGB1. In the multi-organ failure group, neutrophils, monocytes, and HMGB1 levels were higher, while lymphocytes were reduced. Metabolomic analysis revealed 28 metabolites correlated with HMGB1, among which 12-HPETE, asparagine, lactic acid, and carbamyl-aspartate showed the most notable changes. These representative metabolites reflect HMGB1-associated shifts in inflammation and energy metabolism. HMGB1 elevation was further confirmed in SD rats, and its blockade alleviated lung inflammation. Consistently, C-reactive protein (CRP) and procalcitonin (PCT) levels were also increased, supporting the link between HMGB1 and systemic inflammation. CONCLUSION: HMGB1 levels rise sharply in AB pneumonia-especially in patients with MODs-and correlate with inflammatory and hypoxic metabolic shifts. Anti-HMGB1 treatment in SD rats reduced lung inflammation and injury, highlighting HMGB1's potential as a diagnostic biomarker and therapeutic target.