Deoxyribonuclease Is a Potential Counter Regulator of Aberrant Neutrophil Extracellular Traps Formation after Major Trauma

Introduction. Neutrophil extracellular traps (NET) consist of a DNA scaffold that can be destroyed by Deoxyribonuclease (DNase). Thus DNases are potential prerequisites for natural counter regulation of NETs formation. In the present study, we determined the relationship of NETs and DNase after major trauma. Methods. Thirty-nine major trauma patients, 14 with and 25 without sepsis development were enrolled in this prospective study. Levels of cell-free (cf)-DNA/NETs and DNase were quantified daily from admission until day 9 after admission. Results. Levels of cf-DNA/NETs in patients who developed sepsis were significantly increased after trauma. In the early septic phase, DNase values in septic patients were significantly increased compared to patients without sepsis (P < 0.05). cf-DNA/NETs values correlated to values of DNase in all trauma patients and patients with uneventful recovery (P < 0.01) but not in septic patients. Recombinant DNase efficiently degraded NETs released by stimulated neutrophils in a concentration-dependent manner in vitro. Conclusions. DNase degrades NETs in a concentration-dependent manner and therefore could have a potential regulatory effect on NET formation in neutrophils. This may inhibit the antibacterial effects of NETs or protect the tissue from autodestruction in inadequate NETs release in septic patients

Effects of low-dose beraprost sodium, a stable PGI_2 analogue, on reperfusion injury to rabbit lungs

Recent experimental research has either focused on the role of accidental hypothermia as part of the lethal triad after trauma or tried to elucidate the effects of therapeutically induced hypothermia on the posttraumatic course. Induced hypothermia seems to reduce the mortality in experimental models of trauma-haemorrhage. As potential mechanisms, a decrease of cellular metabolism, beneficial effects on haemodynamic function and an attenuation of the inflammatory response have been described. However, negative side effects of hypothermia have to be considered, such as impairment of the coagulatory function and immunosuppressive effects. Furthermore, the optimal strategy for the induction of hypothermia (magnitude, duration, timing, cooling rate, etc.) and subsequent rewarming remains unclear. Nevertheless, this piece of information is essential before considering hypothermia as a treatment strategy for severely injured patients. This review aims to elaborate the differences between accidental and induced hypothermia and to summarize the current knowledge of the potential therapeutic use of induced hypothermia suggested in porcine models of trauma-haemorrhage

Circulating growth/differentiation factor 15 is associated with human CD56 natural killer cell dysfunction and nosocomial infection in severe systemic inflammation

BACKGROUND Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. METHODS NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. FINDINGS During systemic inflammation, the expression of the IL-12 receptor β2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor β receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor β2 expression on NK cells and was enhanced in patients who later acquired septic complications. INTERPRETATION GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. FUND: The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen