Diurnal Variation of Circulating Interleukin-6 in Humans: A Meta-Analysis

The pleiotropic cytokine interleukin-6 (IL-6) has been proposed to contribute to circadian regulation of sleepiness by increasing in the blood at night. Earlier studies have reported diurnal variation of IL-6, but phase estimates are conflicting. We have therefore performed a meta-analysis on the diurnal variation of circulating IL-6. Studies were included if they reported IL-6 in plasma or serum recorded at least twice within 24 hours in the same individual. A systematic search resulted in the inclusion of 43 studies with 56 datasets, for a total of 1100 participants. Individual participant data were available from 4 datasets with a total of 56 participants. Mixed-effects meta-regression modelling confirmed that IL-6 varied across the day, the most conspicuous effect being a trough in the morning. These results stand in contrast to earlier findings of a peak in the evening or night, and suggest that diurnal variation should be taken into account in order to avoid confounding by time of day in studies of IL-6 in plasma or serum.