Shift Work in Rats Results in Increased Inflammatory Response after Lipopolysaccharide Administration

Abstract

The suprachiasmatic nucleus (SCN) drives circadian rhythms in behavioral and physiological variables, including the inflammatory response. Shift work is known to disturb circadian rhythms and is associated with increased susceptibility to develop disease. In rodents, circadian disruption due to shifted light schedules (jet lag) induced increased innate immune responses. To gain more insight into the influence of circadian disruption on the immune response, we characterized the inflammatory response in a model of rodent shift work and demonstrated that circadian disruption affected the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. Since food consumption is a main disturbing element in the shift work schedule, we also evaluated the inflammatory response to LPS in a group of rats that had no access to food during their working hours. Our results demonstrated that the shift work schedule decreased basal TNF-α levels in the liver but not in the circulation. Despite this, we observed that shift work induced increased cytokine response after LPS stimulation in comparison to control rats. Also, Kupffer cells (liver macrophages) isolated from shift work rats produced more TNF-α in response to in vitro LPS stimulation, suggesting important effects of circadian desynchronization on the functionality of this cell type. Importantly, the effects of shift work on the inflammatory response to LPS were prevented when food was not available during the working schedule. Together, these results show that dissociating behavior and food intake from the synchronizing drive of the SCN severely disturbs the immune response.

Circadian rhythms accelerate wound healing in female Siberian hamsters

“…Cytokine and sickness responses are also altered following disruption of the circadian timing system (lesions: Wachulec et al, 1997; Guerrero-Vargas et al, 2014; disruptive light treatments: Prendergast et al, 2015; simulated shift work: Guerrero-Vargas et al, 2015). CRs in immunity are not limited to innate immune responses: T cell-dependent inflammation (a measure of the adaptive immune response) is greater when antigen exposure occurs during the rest as compared to the active phase ( Pownall et al, 1979).…”

Interaction between the hypothalamus and the immune system

“…First, the SCN can set day-night differences in the intensity of the temperature and cytokine responses after the same LPS stimulus (Guerrero-Vargas et al 2014). Second, activation of the SCN after an LPS challenge probably serves to inhibit the inflammatory response, explaining why lesioning the SCN and disturbed circadian rhythmicity, such as that seen in animal models of shift work (see below), result in exacerbated inflammatory responses (Castanon-Cervantes et al 2010;Puttonen et al 2011;Guerrero-Vargas et al 2015).…”

“…), which modifies the magnitude of the immediate response to an inflammatory stimulus (Guerrero‐Vargas et al . , ).…”

“…; Guerrero‐Vargas et al . , ). See Dampney () for more detailed information on these types of hypothalamic–autonomic interactions.…”

A circadian based inflammatory response – implications for respiratory disease and treatment

“…In rodents exposed to simulated shift-work with work and feeding during the day, which corresponds to their usual rest and fasting period, and inactivity and fasting at night (usual active feeding period), there is an uncoordinated inflammatory response to LPS challenge, resulting in elevated cytokine levels and increased mortality (Castanon-Cervantes et al 2010;Adams et al 2013;Guerrero-Vargas et al 2015). Interestingly, if feeding time is restricted to the night time and normal active phase then the immune response is not dysregulated when undergoing LPS challenge.…”