Moderate hypothermia blunts the inflammatory response and reduces organ injury after acute haemorrhage

Background: Reduced body temperature is a common companion to trauma /haemorrhage. Several clinical studies have identified hypothermia as an independent risk variable predisposing to increased morbidity and mortality. At the same time it is known that most enzymatic reactions are downregulated at temperatures below 37 degreesC. Theoretically this should restrain the inflammatory response and protect the host from remote organ injury The study was performed to test this hypothesis. Methods: Twenty-six male Sprague Dawley rats were used for the experiments. Volume controlled haemorrhagic shock was induced by withdrawal of 2.5 ml blood/100 g body weight over 10 min. Half of the animals (n=13) were then cooled to 32.5-33 degreesC, the other half (n=13) were kept normothermic (37.5 +/- 0.5 degreesC). Seventy-five minutes after initiation of bleeding, two-thirds of the blood was retransfused. Thereafter the rats were observed for 2 h. Key substances of systemic inflammation were determined (plasma values of TNF-alpha, IL-6, IL-10, and corticosterone; reactive oxygen species in peritoneal phagocytes), plasma markers of organ function and integrity (AST, ALT, alpha GST, creatinine, urea), and survival. Results: Hypothermia reduced the release of IL-6 (P <0.01). The reductions of plasma levels of TNF alpha (P=0.07) and IL-10 (P= 0.09) were less clear-cut. The release of reactive oxygen species diminished (P <0.01). Organ injury was ameliorated, as reflected by decreased levels of AST (P <0.01), alpha GST (P <0.01), and creatinine (P <0.01). Both groups experienced an almost identical increase of plasma corticosterone. None of the hypothermic rats died, compared to two normothermic. Conclusion: Moderate hypothermia had an organ protective effect in this model of controlled haemorrhagic shock. This coincided with a significant reduction of the proximal cytokine IL-6 and reactive oxygen species, which conceivably influenced the outcome.