Hypothermia Augments NF-kappaB Activity and the Production of IL-12 and IFN-gamma

ABSTRACTBackgroundThe differentiation of Th1 and Th2 is strictly regulated by humoral and cellular factors. The imbalance between Th1 and Th2 is considered to be the pathogenesis of allergic and autoimmune disorders. It is important to elucidate the effect of environmental factors, such as temperature, on the expression of cytokines of Th1 and Th2.MethodsWe investigated the expression of IFN-gamma, IL-4, IL-5, IL-10 and IL-12 from LPS- or PHA-stimulated PBMCs at 30°C or 37°C using ELISA and Real-time PCR. We measured the change of NF-kappaB activity at 30°C or 37°C with LPS stimulation using the reporter gene assay.ResultsIFN-gamma production from LPS-stimulated PBMCs at 30°C was up-regulated compared with 37°C. IL-5 and IL-10 production from PHA-stimulated PBMCs at 30°C were down-regulated compared with 37°C. This augmented IFN-gamma production was caused by the up-regulation of IL-12 production from CD14+ blood monocytes. Both IL-12 mRNA and IL12 protein at 30°C were up-regulated compared with 37°C. NF-kappaB, the key molecule for the expression of IL-12, was also augmented at 30°C compared with 37°C.ConclusionsHypothermia up-regulated the expression of IL-12 and IFN-gamma due to the augmented NF-kappaB activity. It is suggested that hypothermia modifies the pattern of cytokine gene expression.