Flow chart showing participation in the study.

<p>Flow chart showing participation in the study.</p

Descriptive statistics for distance travelled, sleepiness and sleep duration for night workers (NW) and non-night workers (NNW).

*<p>shown per 24 h period.</p

Adjusted odds ratio for variables associated with lane crossing.

*<p>variables were entered simultaneously into the model.</p>**<p>shown per 24 h.</p

Data and fitted time courses, showing the last 26 out of 56 datasets.

<p>Data are shown as estimated from original publications, with error bars showing standard deviations. Y axes show ln IL-6 (pg/ml) throughout. Hours are in chronological time where 1 is 01:00 on the first day. Red lines show predictions from the best-fitting model.</p

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

<div><p>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.</p></div

Data inclusion.

<p>Some of the 43 included studies contained more than one dataset. The final number of datasets was 56 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165799#pone.0165799.t001" target="_blank">Table 1</a>).</p

Individual participant data.

<p>Individual participant data were available from four datasets and are shown here mainly for the purpose of illustrating the high degree of variability within individuals. To illustrate summary effects within each dataset, thick lines show loess functions fitted to each dataset. Time from 22:00 to 07:00 is shaded to indicate the night. For Lekander 2013, two sets of measurements, made with a few days’ interval, have been plotted over the same time course, in red and blue respectively.</p

Predicted diurnal time courses from meta-regression models.

<p>Left: Best-fitting model including cosinor functions with 24 and 12 h periods. Right: Model including only 24 h period. Time from 22:00 to 07:00 is shaded to indicate the night.</p

Mixed model ANOVA.

<p>Footnote: KSS = Karolinska Sleepiness Scale, LP = lateral position, SDLP = standard deviation of lateral position, B-ORS = behavioural signs of observer rated sleepiness, D-ORS = driving impairment related observer rated sleepiness, Session (df = 2):before lunch, after lunch, night) and Time (df = 17) (minute 1–45 and 65 to 105). F and p-values. Significant values in bold.</p

Observers (O) allocation over the three driving sessions.

<p>Observers (O) allocation over the three driving sessions.</p