C-reactive protein (CRP)
The acute phase proteins are nonspecific biochemical markers produced by hepatocytes in response to tissue injury, infection, or inflammation. Interleukin (IL)-6 is a potent inducer of acute phase proteins that can include proteinase inhibitors, coagulation and complement proteins, and transport proteins. Clinically, only C-reactive protein (CRP) has been consistently used as a marker of injury response due to its dynamic reflection of inflammation. Importantly, CRP levels do not show diurnal variations and are not affected by feeding. Only pre-existing liver failure will impair CRP production. Therefore, it has become a useful biomarker of inflammation as well as response to treatment. Its accuracy surpasses that of the erythrocyte sedimentation rate.
Which of the following is true regarding the inflammatory response following traumatic injury?
The degree of the systemic inflammatory response following trauma is proportional to injury severity and is an independent predictor of subsequent organ dysfunction and resultant mortality. Recent work has provided insight into the mechanisms by which immune activation in this setting is triggered. The clinical features of the injury-mediated systemic inflammatory response, characterized by increased body temperature, heart rate, respirations, and white blood cell count, are similar to those observed with infection. While significant efforts have been devoted to establishing a microbial etiology for this response, it is now widely accepted that systemic inflammation following trauma is sterile.
High-mobility group protein B l (HMGB l )
The best-characterized DAMP in the context of the injuryassociated inflammatory response is high-mobility group protein Bl (HMGBl), which is rapidly released into the circulation within 30 minutes following trauma. Subsequent studies have proven, however, that HMGBl is actively secreted from immune-competent cells stimulated by PAMPs (eg, endotoxin) or by inflammatory cytokines (eg, tumor necrosis factor and interleukin -1). Stressed nonimmune cells, such as endothelial cells, and platelet also actively secrete HMGBI. Finally, passive release of HMGBl can occur following cell death, whether it is programmed or uncontrolled (necrosis). The diverse pro inflammatory biological responses that result from HMGBl signaling include: (1) the release of cytokines and chemokines from macrophage/monocytes and dendritic cells; (2) neutrophil activation and chemotaxis; (3) alterations in epithelial barrier function, including increased permeability; and (4) increased procoagulant activity on platelet surfaces; among others.
The most abundant amino acid in the human body is
Glutamine is the most abundant amino acid in the human body, comprising nearly two-thirds of the free intracellular amino acid pool.
What is the role of mitochondrial DAMPs in the injurymediated inflammatory response?
Mitochondrial proteins and/or DNA can act as DAMPs by triggering an inflammatory response to necrosis and cellular stress. Specifically, the release of mitochondrial DNA (mtDNA) and formyl peptides from damaged or dysfunctional mitochondria has been implicated in activation of the macrophage inflammasome, a cytosolic signaling complex that responds to cellular stress. With stress or tissue injury, mtDNA and peptides are released from damaged mitochondria where they can contribute to a sterile inflammatory response. From an evolutionary perspective, given that eukaryotic mitochondria derive from bacterial origin, it would make sense that they retain bacterial features capable of eliciting a strong response that is typically associated with a pathogen trigger.
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