Immunomodulatory effects of mild hypothermia onto the pulmonary inflammatory response following multiple trauma in sus scrofa

Background Immunomodulatory effects and mechanisms of mild hypothermia in patients receiving protective mechanical ventilation suffering from polytrauma remain widely unclear. We hypothesized, that mild controlled hypothermia would modulate the pulmonary inflammatory reaction in a porcine polytrauma model with hemorrhagic shock, including blunt chest trauma, penetrating abdominal trauma and muscoskeletal limb injury with a prolonged post-traumatic observational phase of 48 hours.

Methods A standardized polytrauma was induced including blunt chest trauma, liver laceration and muscoskeletal lower leg injury as well as two degrees of blood loss (45 and 50%) with prolonged phases of shock for 90 (n = 30) and 120 min. (n = 20) respectively [1]. The pigs, including a sham group (n = 10), were randomized to either hypothermia (33 °C, HT) or normothermia (38 °C, NT), then underwent intensive care treatment for an observational period of 48 hours. Subsequently, we evaluated BAL-fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis.

Results Following trauma and shock, a significant increase of IL-6 RNA in lung tissue was observed in both trauma groups. Likewise, an increased IL-6 concentration could be detected in BAL-fluid, with a relative lower increase of IL-6 in pigs treated with hypothermia following severe shock versus normothermia-controls. However, the therapy trial by hypothermia did not lead to an overall reduction of IL-6 expression or release but showed a significant increase of IL-6 RNA in lung tissue. It also had no significant effect on cytokine levels of Interleukin-1 beta, Interleukin-10 or Angiopoietin-2, expression of NFKBIA, SP-C or COX-2 or microRNAs 146a and 155 or tissue apoptosis quantified by Western Blot of Caspase-3.

Conclusion Mild hypothermia could not show a significant benefit onto the pulmonary inflammatory response during the first 48 hours following multiple trauma. Further studies with a focus on multi-organ failure after trauma are required to investigate the impact of mild hypothermia on lung inflammation and function in multiple trauma patients, ideally over a prolonged observational period.

• Reference

• 1 Eschbach et al. Eur J Med Res 2015; 20: 73 doi:10.1186/s40001-015-0162-0