Moderate hypothermia delays proinflammatory cytokine production of human peripheral blood mononuclear cells*

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Abstract
To clarify the influence of moderate hypothermia on the production of proinflammatory cytokines. Controlled in vitro study. Research laboratory. Peripheral blood mononuclear cells from healthy adult human subjects. Stimulation with 1 μg/mL lipopolysaccharide at 33°C and 37°C. Concentrations of released tumor necrosis factor-α, interleukin-1β, and interleukin-6 were measured chronologically by enzyme immunoassay. The number of mRNA copies of these cytokines was determined by competitive reverse transcriptase-polymerase chain reaction analysis, and nuclear factor-κB activations were assessed by electrophoretic mobility shift assay. Significant reduction of the released-tumor necrosis factor-α concentration was observed 1 and 2 hrs after the stimulation with lipopolysaccharide at 33°C compared with 37°C. The peak release of interleukin-1β at 33°C was delayed 12 hrs later than that at 37°C. A delayed peak in the release of interleukin-6 also was observed at 33°C. The peaks of cytokines were confirmed at the mRNA expression level by competitive reverse transcriptase-polymerase chain reaction analysis at both temperatures. The peak of the tumor necrosis factor-α mRNA expression level was observed at 1 hr after the stimulation at 37°C and 2 hrs after the stimulation at 33°C. In the interleukin-1β mRNA expression, at 37°C the first peak appeared 1 hr and the second 6 hrs after the stimulation. In contrast, at 33°C, the first peak appeared 2 hrs and the second 12 hrs after the stimulation. Whereas interleukin-6 mRNA expression at 37°C peaked 6 hrs after the stimulation, no definite peak was observed at 33°C and the expression level was approximately half of that at 37°C. The maximum intensity of nuclear factor-κB activation at 33°C was delayed by 1.5 hrs compared with that at 37°C. Moderate hypothermia delays the induction of proinflammatory cytokines in human peripheral blood mononuclear cells.