Uncovering Novel Biomarkers of Inflammation as Potential Screening Targets of Disease Risk in Healthcare Shift Workers: A Pilot Study.

Shift work, experienced by nearly 30% of the U.S. workforce, is hazardous to health and has become a pervasive labor practice in the healthcare sector worldwide. It increases the risk of stroke, diabetes, cancer, and cardiovascular disease. Nonetheless, specific screening targets for shift workers still need to be defined. In this study, we have begun uncovering these targets as specific low-grade systemic inflammation markers and functional endotoxin-elicited responses that may foreshadow disease risk in shift workers. One hundred four participants (normothermic and normotensive) were healthy, non-smoking, and drug- and medication-free volunteers recruited from Atlanta area hospitals and medical schools. We assessed the concentration of three proteins in plasma samples from day workers and shift workers (lipopolysaccharide-binding protein, IL-10, and TNF-α), and the relationship between these baseline biomarkers and their response to an ex-vivo endotoxin challenge. We show that shift work increases low-grade systemic inflammation and disrupts discrete endotoxin responses. As shift work exposure increases, the correlation between low-grade systemic inflammation markers and their endotoxin responses was disrupted; this effect was more robust for TNF-α than for IL-10. With increased shift work exposure, these events, alone or combined, represent potential systemic and functional signals that may be harnessed to develop screening tools to identify at-risk individuals.

Shift Work Predicts Increases in Lipopolysaccharide-Binding Protein, Interleukin-10, and Leukocyte Counts in a Cross-Sectional Study of Healthy Volunteers Carrying Low-Grade Systemic Inflammation.

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-1ß, 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.