Impaired Responses to In Vitro Lipopolysaccharide-Induced Stimulation After Long-Term, Rotating Shift Work.

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.