Fig. 1.

Damage Associated Molecular Patterns (DAMPs) release and immune cell activation following sterile traumatic injury. Tissue damage arising from traumatic or thermal injury results in the release into circulation of mitochondrial (e.g. mtDNA, formyl peptides), cytosolic (e.g. F-actin) and nuclear (e.g. HMGB1)-derived damage associated molecular patterns (DAMPs). Through binding to pathogen recognition receptors, DAMPs trigger the activation of circulating immune cells resulting in the secretion of pro- and anti-inflammatory cytokines as well as a series of functional responses, which include the generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Together, cell activation and cytokine secretion creates an inflammatory environment that favours the development of multiple organ failure, tissue damage and immunoparesis, conditions that are associated with a range of poor patient outcomes, which include a longer length of hospital stay and an increased risk of sepsis and mortality. Tissue damage arising from immune cell activation would lead to the release of further DAMPs, creating a vicious cycle, with continued inflammation and immune activation. ATP adenosine tri phosphate, DAMP damage-associated molecular pattern, F-actin filamentous actin, HMGB1 high-mobility group box 1 protein, IL interleukin, LOS length of stay, MCP-1 monocyte chemoattractant protein 1, MOF multiple organ failure, mtDNA mitochondrial DNA, NETs neutrophil extracellular traps, ROS reactive oxygen species, SIRS systemic inflammatory response syndrome, TNF-α tumour necrosis factor-alpha