Warming to 39°C but Not to 37°C Ameliorates the Effects on the Monocyte Response by Hypothermia

OBJECTIVE:To investigate whether warming to normal body temperature or to febrile range temperature (39°C) is able to reverse the detrimental effects of hypothermia. BACKGROUND:Unintentional intraoperative hypothermia is a well-described risk factor for surgical site infections but also sepsis. We have previously shown that hypothermia prolongs the proinflammatory response whereas normothermia and especially febrile range temperature enhance the anti-inflammatory response. METHODS:Primary human monocytes were isolated from healthy volunteers. After stimulation with LPS (Lipopolysaccharide), the monocytes were exposed to 32°C for 3 hours or 6 hours and then warmed at either 37°C or 39°C for the remaining 33 hours or 36 hours, respectively. Tumor necrosis factor α, interleukin 10, and the expression of miR-155 and miR-101 were assessed at 24 hours and 36 hours. RESULTS:Warming to 37°C does not normalize monocyte cytokine secretion within 36 hours, whereas warming to 39°C partially reverses the effects of hypothermia on monocyte function. Both miR-155 and miR-101 were suppressed after the warming episode. However, 39°C had a stronger suppressive effect than 37°C. The duration of hypothermia and the warming temperature seem to be critical for a full reversibility of the effects of hypothermia. CONCLUSION:Warming to normal body temperature (37°C) does not restore normal monocyte function in vitro. These data suggest that hypothermic patients should be warmed to febrile range temperatures. Furthermore, febrile range temperatures should be investigated as a means to modulate the inflammatory response in patients with systemic infections.