Trauma-Induced Damage-Associated Molecular Patterns-Mediated Remote Organ Injury and Immunosuppression in the Acutely Ill Patient

Abstract

Trauma is one of the leading causes of death and disability in the world. Multiple trauma or isolated traumatic brain injury are both indicative of human tissue damage. In the early phase after trauma, damage-associated molecular patterns (DAMPs) are released and give rise to sterile systemic inflammatory response syndrome (SIRS) and organ failure. Later, protracted inflammation following sepsis will favor hospital-acquired infection and will worsen patient's outcome through immunosuppression. Throughout medical care or surgical procedures, severe trauma patients will be subjected to endogenous or exogenous DAMPs. In this review, we summarize the current knowledge regarding DAMP-mediated SIRS or immunosuppression and the clinical consequences in terms of organ failure and infections.

Keywords: critical care; damage-associated molecular pattern; hospital-acquired infection; posttraumatic immunosuppression; remote organ dysfunction; transfusion.

Figure 1

Pathway activation after damage-associated molecular patterns (DAMPs) stimulation. DAMPs are recognized by surface or endosomal TLRs and trigger either TRIF and NF-κB activation. TLR4, toll-like receptor 4; TIR, toll/interleukin-1 receptor; DNA, desoxyribonucleic acid; RNA, ribonucleic acid; IRF, interferon regulatory factor; TRIF, TIR domain-containing adaptor protein inducing interferon β; NF-κB, nuclear factor κB; NEMO, NF-κB essential modulator; IRAK, IL-1 receptor-associated kinase-4; MyD88, myeloid differentiation protein 88; RAGE, receptor for advanced glycation end products; HMGB1, high-mobility group box 1; HSP, heat-shock protein; IKK, Iκ-B kinase.

Figure 2

Adenosine effects on dendritic and T cells during trauma. G protein-coupled surface receptors (GPCR) are key actors of Adenosine mediated inflammatory after trauma. A2AR receptors are expressed on many subsets including Regulatory T cells, effector T cells, and dendritic cells. ATP, adenosine 5’-triphosphate; CD39, nucleoside triphosphate diphosphohydrolase-1; CD73, surface-expressed ecto-5′-nucleotidase; A2AR, adenosine A2A receptor.

Figure 3

Damage-associated molecular patterns (DAMPs) effect overview on remote organ dysfunction after trauma. After severe trauma, multiple DAMPs are released and can trigger lung edema or kidney tubular epithelium activation. Besides, subsequent transfusion, fluid resuscitation and surgery will worsen these phenomenon and lead to remote acute organ failure. ALI, acute lung injury; ARDS, acute respiratory distress syndrome; CARS, compensatory anti-inflammatory response; PMN, polymorphonuclear leukocytes; MTD, mitochondrial damage-associated molecular patterns; RBP4, retinol-binding protein-4; PS100, protein S100; HSP, heat-shock protein; TNFR1, Type 1-TNF receptor; TNF-α, tumor necrosis factor-α; HMGB1, high-mobility group box 1.