Abstract
Background
Infections are frequent in critically ill patients with earthquake‐associated crush injury (CI) and contribute to poor outcomes, yet the immune pathways underlying posttrauma susceptibility remain poorly defined. We investigated longitudinal changes in damage‐associated molecular pattern (DAMP)/PAMP sensing and downstream inflammatory programs in CI patients requiring intensive care.
Methods
Nineteen CI patients admitted to the ICU after the February 6, 2023 Kahramanmaraş earthquake and 18 age‐ and sex‐matched healthy controls were enrolled. Peripheral blood was collected on hospital days 7 and 21. DAMP/PAMP receptor expression was assessed by flow cytometry and RT‐qPCR, and pathway activation was evaluated by phospho‐flow (pSTING, pIRF3, pNF‐κB, and p‐cJun) in gated lymphocytes and monocytes. Plasma cytokines/alarmins and select DAMPs were quantified by multiplex enzyme‐linked immunosorbent assay (ELISA)/assays.
Results
CI patients demonstrated broad remodeling of nucleic acid‐sensing programs, including reduced expression of TLR7, STING, and IRF7, with a discordant signaling pattern characterized by increased IRF3 phosphorylation, transiently reduced pSTING, and sustained reduction of p‐cJun, while NF‐κB activation remained comparatively stable. In plasma, IL‐33 and IFN‐α2 were reduced on Day 7, and type 3 immunity‐associated cytokines IL‐23 and IL‐17A were significantly decreased by Day 21, consistent with impaired antimicrobial barrier‐supporting responses. Circulating DAMPs were dynamically altered, with increased S100A9 and HMGB1 and decreased ATP following injury.
Conclusions
Earthquake‐associated CI is associated with dynamic DAMP release and dysregulated innate sensing accompanied by suppression of antiviral and type 3 immune cytokine programs. These immune alterations may contribute to heightened vulnerability to secondary infections in critically ill CI patients.