Shock. 2026 Aug 17. doi: 10.1097/SHK.0000000000002926. Online ahead of print.
ABSTRACT
Over the past five decades, advances in acute burn care have markedly improved early survival following severe thermal injury. However, long-term epidemiologic studies demonstrate that burn survivors remain at increased risk for metabolic disease, cardiovascular pathology, malignancy, cognitive impairment, and accelerated aging, well beyond wound closure. These observations suggest that severe burn injury can initiate a chronic disease state characterized by persistent physiologic dysregulation in a subset of patients. Emerging evidence indicates that this phenotype is driven by sustained immunometabolic dysfunction, in which immune and metabolic pathways are tightly coupled and mutually reinforcing. Severe burn injury induces durable reprogramming of innate and adaptive immune cells alongside prolonged hypermetabolism, mitochondrial dysfunction, and neuroendocrine stress signaling. This results in a persistent inflammatory, immunosuppressed, catabolic syndrome (PIICS), where chronic inflammation coexists with impaired adaptive immunity and ongoing amino acid depletion. In this review, we synthesize population-based, clinical, and experimental data supporting burn injury as a chronic immunometabolic disease. We highlight key mechanisms linking immune dysfunction with altered substrate utilization, mitochondrial bioenergetics, and neuroimmune signaling, and discuss how these pathways contribute to long-term organ dysfunction. Finally, we outline emerging opportunities for risk stratification and therapeutic interventions targeting integrated immunometabolic pathways.
PMID:42606951 | DOI:10.1097/SHK.0000000000002926