Night work effects on salivary cytokines TNF, IL-1β and IL-6

Abstract

Shift work is unavoidable in modern societies, but at the same time disrupts biological rhythms and contributes to social distress and disturbance of sleep, health and well-being of shift workers. Shift work has been associated with some chronic diseases in which a chronic inflammatory condition may play a role. However, few studies investigating the association of cytokine and other inflammation markers with shift workers have been published in recent years. In this study we evaluated the effects of permanent night work on the production of tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6 and melatonin in saliva. Another aim was to demonstrate the benefit of the use of salivary cytokines for studies in chronobiology, since it is an easy and non-invasive method that allows for sampling at several times. Thirty-eight healthy male workers, being 21 day workers and 17 night workers, agreed to participate in this study. Sleep was evaluated by actigraphy and activity protocols. Saliva was collected during three workdays approximately at the middle of the work shift and at bed and wake times of the main sleep episode. Saliva samples were then analyzed by enzyme-linked immunosorbent assay to measure TNF, IL-1β, IL-6 and melatonin levels, and the results were submitted to non-parametric statistical analysis. The use of saliva instead of blood allowed for a greater number of samples from the same subjects, allowing identifying alterations in the daily production patterns of salivary cytokines TNF, IL-1β and IL-6 that probably are linked to night work. Salivary TNF and IL-1β levels were similar for day and night workers, with higher daily production after awakening, in the morning hours for day workers and in the afternoon for night workers. Both groups presented a significant daily variation pattern of these two cytokines. Day and night workers produced similar amounts of salivary IL-6. Nevertheless, the daily variation pattern observed among day workers, with a peak after awakening, was absent among night workers. Thus, in our study, night workers showed partially adjusted daily variation patterns for salivary TNF and IL-1β, not seen for salivary IL-6. Results for salivary IL-6 could be better explained as a consequence of circadian disruption due to permanent night work. Our results suggest that the whole circadian system, including clocks and pineal gland, is involved in regulating cytokine profile in shift workers and that a coordinated production of these cytokines, important for an adequate inflammatory response, could be disturbed by shift work. The distinct effects that shift work may have on different cytokines could give some cues about the mechanisms involved in this association.

Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation

“…Briefly, the normal rhythmic secretion of melatonin can guarantee sufficient levels of serum concentration required for an anti-inflammatory effect. It was also found that night work can disturb the secretion of melatonin in healthy male workers, resulting in the lift of TNF, IL-1 and IL-6 in their saliva [30]. In the present study, melatonin could promote COL2 and aggrecan synthesis and inhibit MMP-3 production.…”

A critical review of melatonin assays: Past and present

“…Melatonin levels in saliva collected at midday in normal children were between 6 and 11 pg/mL with this assay while the threshold for calculating DLMO in adults was 10.4 pg/mL . Some recent studies have however reported levels of 0.8‐2 pg/mL in adults at 14:00 hours . The reasons for this inter‐laboratory variation are not known.…”

“…74 Some recent studies have however reported levels of 0.8-2 pg/mL in adults at 14:00 hours. 75,76 The reasons for this inter-laboratory variation are not known.…”

Sleep in the United States Military

“…The consequence of this misalignment is a heightened pro-inflammatory response exclusively due to the phase-shift in the light-dark cycle, rather than concurrent sleep loss [158]. Regimens of ECD also impact metabolic processes on whole-body, macroscopic [159] and microscopic scales (heart [160]; skeletal muscle [161]; liver [162]) similar to what has been reported in human models of sleep loss compounded by shift work [54, 163, 164]. Animal models of constant light and constant darkness can desynchronize the suprachiasmatic nucleus (SCN) and alter gene activity [68, 69], and can further our understanding of the consequences of extended shift work and night operations in military personnel.…”