Effects of hypothermia and re-warming on the inflammatory response in a murine multiple hit model of trauma

Introduction: Although, hypothermia is a frequent event after trauma, it is unclear whether its beneficial or detrimental effects are more important. This study aims to quantify the effects of hypothermia and re-warming on the inflammatory response after fracture/hemorrhage and subsequent fracture stabilization with resuscitation. Materials and methods: Eighty-one male C57Bl/6 mice (aged 8-10 weeks, weighing 22.0 ± 3.0 g) underwent femoral fracture and hemorrhage followed by resuscitation and splint fixation of the fracture. Animals were sacrificed 3 h after induction of hemorrhage and fracture. Besides a sham group (n = 6), four experimental groups were created: A: normothermia (n = 12), B: hypothermia after trauma (n = 21), C: re-warming after resuscitation and before stabilization (n = 21), and D: hypothermia before trauma (n = 21). Groups B-D were further subdivided into three subgroups according to the degree of hypothermia (subgroup 1: 35-33°C, subgroup 2: 32.9-30.0°C, and subgroup 3: 29.9-27.0°C). Plasma cytokine (TNF-α, IL-6, and IL-10) and chemokine (MCP-1) concentrations were determined by ELISA, pulmonary permeability changes were quantified, and histological analysis of lung and liver tissues was performed. Results: Normothermia resulted in a significantly increased early mortality rate. A significantly increased pro-inflammatory and decreased anti-inflammatory responses were also observed in normothermia as compared to hypothermia. The extent of these changes was most pronounced in the severe hypothermic group. Re-warming after mild hypothermia resulted in a pro-inflammatory response comparable to normothermia. Conclusion: Hypothermia has a beneficial effect on early survival after trauma, which appears to be independent of the level of hypothermia and re-warming. Re-warming, however, enhanced the pro-inflammatory response. Further studies with a longer posttraumatic observation period are required to investigate the long term effects of the hypothermia and re-warming-induced changes on the pro- and anti-inflammatory responses.