Does clinically relevant temperature change miRNA and cytokine expression in whole blood?

Unintentional hypothermia is a well-described risk factor for death and complications after elective and emergency surgery. The molecular mechanisms by which hypothermia exerts its detrimental effects are not well understood. Differences in cytokine production and the overall cell function have been reported under hypothermic conditions. We investigated the effect of a range of clinically relevant temperatures on cytokine production and microRNA (miRNA) expression in a whole-blood model. We found that there was a wide variation in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10 production among different subjects, ranging from low to high TNF-α producers. The intersubject variation can also be found on the transcriptional level: high producers had higher upregulation of TNF-α messenger RNA than intermediate and low producers. This variation in TNF-α was reproducible in each individual. Temperature seems to modulate TNF-α production among these different groups. miRNA expression was modulated by temperature. miRNA-181a might control, or be a part of the mechanism which controls, TNF-α production. However, an analysis of whole-leukocyte RNA does not allow the investigation of mechanisms in a specific leukocyte subpopulation such as monocytes, because these changes may be concealed by miRNA expression changes in the other leukocyte subsets. In conclusion, TNF-α, IL-6, and IL-10 production is highly variable among different persons, but temperature affects the expression of miRNAs, which may consequently alter the production of TNF-α.