Oscar Castanon-Cervantes

Shift work is a common labor practice affecting nearly 30% of the U.S. workforce. Long-term, rotating-shift work is particularly harmful to health. Persistent sleep deprivation in shift workers, among other factors, facilitates the development of a state of subclinical but chronic systemic inflammation with a high incidence and prevalence of infections and inflammation-related pathologies, suggesting an underlying disruption of immune responses. However, despite this state of chronic immune activation, cell-mediated inflammatory responses in rotating-shift workers are poorly understood. Here, we used lipopolysaccharide (LPS) to stimulate peripheral blood mononuclear cells (PBMCs) isolated from rotating-shift workers and healthy day-shift workers and investigate their immune responses. The results showed that PBMCs from rotating-shift workers had a dampened inflammatory response. Specifically, the secretion of LPS-induced TNF-α in culture supernatants was significantly reduced compared to the response found in PBMCs from day-shift workers. However, anti-inflammatory responses, reflected by the secretion of LPS-induced IL-10, were indistinguishable between PBMCs from day-shift and rotating-shift workers. In addition, the correlation between the plasma concentration of lipopolysaccharide-binding protein (LBP, a marker of systemic inflammation) and LPS-induced responses was disrupted only in rotating-shift workers, suggesting that in this group, an impaired mechanism that weakens the relationship between pro- and anti-inflammatory signaling may underlie the hypo-responsiveness of PBMCs. Our results suggest that persistent subclinical systemic inflammation in rotating-shift workers disrupts cell-mediated immunity, increasing the risk of infection and other inflammation-related pathologies in this population.

The disruption of inflammatory responses is a potential mechanism behind the harmful effects of shift work and is associated with increased risk of hypertension, stroke, obesity, diabetes, and cancer. These responses are linked to the proliferation of leukocytes in shift workers, suggesting a systemic signal as a potential mediator. The purpose of this study was to assess the relationship between systemic inflammation, leukocyte counts, and systemic endotoxemia in samples from a diverse cohort of day workers and shift workers. Participants (normothermic and normotensive) were healthy volunteers, non-smoking, and drug- and medication-free. The following outcomes were measured: C-reactive protein, TNF-α, IL-6, IL-1β, IL-10, leukocyte counts (monocytes, lymphocytes, and neutrophils), and lipopolysaccharide-binding protein (LBP). Risk factors that increase systemic inflammation, such as blood pressure, sleep loss, and cortisol, were also assessed. The results indicated that shift workers slept significantly less than day workers and had significantly increased concentrations of all of the cytokines measured as well as plasma cortisol. Regression models found that after controlling for covariates, shift-work exposure predicted the significant increase observed in IL-10, leukocyte counts, and LBP. Our results suggest that acute increases in low-grade systemic endotoxemia are unresolved during chronic shift-work exposure. This ongoing immune challenge may underlie the disrupted inflammatory responses characteristic of shift-work-related pathologies. Systemic endotoxemia may represent a novel target to investigate the early effects of exposure to shift-work schedules.