Serum levels of HSP70 and other DAMP proteins can aid in patient diagnosis after traumatic injury

Abstract

Danger-associated molecular patterns (DAMPs) are activated by endogenous signals that originate from stressed, injured, or necrotic cells, signifying "danger" to the host. In this study, we evaluated the expression of the DAMP heat shock protein 70 (HSP70) in trauma patients with and without secondary infections. Levels of glucose (GLU), procalcitonin (PCT), total cholesterol (T-Chol), and white blood cell (WBC) counts were also evaluated at three time stages after trauma. Our analysis showed that the levels of serum HSP70 in patients with minor, moderate, and severe injuries were significantly higher than in healthy patients at each time point post-injury (P < 0.01), and levels of serum HSP70 in the severe injury group were significantly higher than in the minor injury group at 1-6 h after trauma (P = 0.047). HSP70 was correlated with GLU and was negatively correlated with T-Chol in the period 1-6 h after injury (P = 0.008/0.032). WBC and GLU were elevated after trauma, with mutual positive correlation (P < 0.001). PCT levels increased later than WBC counts and GLU levels; these levels were correlated at the two later time periods, 24-48 h and 60-90 h (P = 0.008/0.041). PCT continued to rise in patients with secondary infection, but PCT dropped at the third time period in patients without secondary infection. In summary, our results suggest that danger and stress theory can be used to predict severity of trauma.

A conceptual time window‐based model for the early stratification of trauma patients

“…It has been found to correlate with injury severity, organ failure, nosocomial infections and mortality . Serum levels of the DAMP heat‐shock protein 70 (HSP70) are elevated in patients with not only severe, but minor and moderate injuries as well, when compared to healthy controls . Mitochondrial DNA (mtDNA) is another DAMP which is released from damaged or dead cells to activate polymorphonuclear neutrophils via TLR‐9 .…”

Microbial recognition and danger signals in sepsis and trauma

“…The expressions of Hsp27, Hsp70 and Hsp90 are significantly increased in patients following traumatic injury, and serum levels of Hsp70 correlate with severity of injury [94, 95]. Elevated serum levels of Hsp70 among patients with severe traumatic brain injury (TBI) are associated with a significant increase in mortality [96].…”

Danger signals in trauma

“…The authors suggest that the extracellular release of the immature HSP60 may be associated with traumatic cell necrosis, and could be involved in the release of NO by immune-competent cells, subsequently inducing an activation of the local inflammatory response [202]. Increased levels of systemic HSP70 at 1–6 h after injury were found in trauma patients, and the magnitude of the increase was related to injury severity and prediction of secondary infection [203]. If HSP70 levels decreased in the period from 60 to 90 h after trauma the patient had a better outcome as compared to those patients without decreased HSP70 levels [203].…”

“…Increased levels of systemic HSP70 at 1–6 h after injury were found in trauma patients, and the magnitude of the increase was related to injury severity and prediction of secondary infection [203]. If HSP70 levels decreased in the period from 60 to 90 h after trauma the patient had a better outcome as compared to those patients without decreased HSP70 levels [203]. An increase in HSP70 levels between the 24–48-h period and the 60–90-h period suggested infection [203].…”

“…If HSP70 levels decreased in the period from 60 to 90 h after trauma the patient had a better outcome as compared to those patients without decreased HSP70 levels [203]. An increase in HSP70 levels between the 24–48-h period and the 60–90-h period suggested infection [203]. As suggested by others, these data support the hypothesis that HSP70 is produced as a danger signal to stimulate the immune systems of trauma patients [204].…”