Diurnal systemic inflammation and resolution processes during sleep restriction and recovery

• Applicant: Dr. Larissa Engert
• Subject Area: Immunology ; Endocrinology, Diabetology, Metabolism
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437206608

Chronic low-grade systemic inflammation is involved in the pathogenesis of many human diseases, such as cancer, chronic pain, cardiovascular, neurodegenerative, and metabolic diseases. Common sleep patterns of restricting sleep during the workweek and catching up on sleep over the weekend induce inflammatory upregulation that does not resolve completely following weekend recovery sleep. The mechanisms causing these human sleep/wake habits to result in inflammatory diseases are poorly understood. However, it is assumed that disrupted diurnal immune function is crucial for disease development. The aim of this research proposal is to investigate underlying diurnal mechanisms of chronic low-grade systemic inflammation and inflammatory resolution in a model of workweek sleep restriction and weekend recovery sleep. It is hypothesized that this sleep pattern leads to an inflammatory imbalance by disrupting the expression and diurnal organization of markers regulating inflammatory homeostasis, including markers of inflammation (e.g., interleukin-6 production by monocytes), classical markers of counter-inflammation (e.g., cortisol), and recently detected markers of inflammatory resolution (e.g., resolvins). In the long term, such disruption of inflammatory homeostasis results in enhanced disease susceptibility. To test this, healthy participants (50% women) will undergo two 11-day in-hospital stays, during which they will be either exposed to sleep restriction (4 hours of sleep per night) followed by recovery sleep or to control sleep (8 hours of sleep per night). Blood samples taken at different times of day to investigate immunological, endocrinological, and molecular markers will be complemented by continuously recorded physiological variables, e.g., autonomic and sleep indices. The blood samples will be used to investigate whether workweek sleep restriction disrupts inflammatory homeostasis, as indicated by an imbalance between markers of inflammation, classical counter-inflammation, and inflammatory resolution. These markers will be investigated with focus on diurnal variations. In addition, functional characteristics of immune cells and molecular pro-resolutory processes will be characterized as completely novel aspects in the investigation of inflammatory consequences of common sleep patterns. This project will contribute to identify mechanisms by which chronic insufficient sleep increases disease susceptibility, thus providing critical knowledge in assessing and improving health and well-being.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Monika Haack, Ph.D.