Diurnale systemische Entzündungs- und Resolutionsprozesse während Schlafrestriktion und Erholungsschlaf

• Antragstellerin: Dr. Larissa Engert
• Fachliche Zuordnung: Immunologie ; Endokrinologie, Diabetologie, Metabolismus
• Förderung: Förderung von 2019 bis 2022
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 437206608

• Erstellungsjahr: 2023

Zusammenfassung der Projektergebnisse

Disrupted or short sleep is known to increase the risk for multiple disease conditions involving immunopathology, including cardiometabolic, neurodegenerative, pain, autoimmune disorders, and cancer. Inflammation is thought to be a mechanism through which inadequate sleep acts as predictor for these chronic diseases. One potential way to mitigate negative health consequences associated with inadequate sleep is to target inflammation. Few studies investigated whether improving sleep affects inflammatory processes, but results suggested that this alone may not be sufficient to mitigate sleep loss-related inflammation. Thus, a complementary approach is to target inflammatory processes pharmacologically. We investigated whether low-dose acetylsalicylic acid (ASA) administered prior to and during exposure to experimental sleep restriction is able to blunt the expected inflammatory response associated with sleep loss. 46 healthy participants (19F/27M) were studied in a randomized crossover trial with three 11-day (10 nights) in-hospital protocols. Each participant was assigned to 1 control stay with daily placebo tablet (PBO) intake and 2 stays with restricted sleep with daily intake of either PBO or low-dose ASA. The in-hospital stays were separated by at least 2 months. Each in-hospital stay started with 2 nights with a sleep opportunity of 8h/night for baseline measurements. Then, under the 2 restricted sleep conditions, participants were exposed to 5 nights of restricted sleep with a sleep opportunity of 4h/night followed by 3 nights of recovery sleep with a sleep opportunity of 8h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the entire protocol. During each inhospital stay, participants had 3 days of intensive monitoring (at baseline, after sleep restriction/control sleep, and after recovery sleep), which included blood sampling and polysomnographic recording. Prior to each in-hospital stay, there was a 2-week at-home monitoring phase, which included actigraphy, sleep diary recording, and daily ASA/PBO intake. The outcome variables to assess inflammation were interleukin (IL)-6 and cyclooxygenase (COX)- 2 expression in monocytes, C-reactive protein (CRP) levels, and immune cell counts. Data were analyzed using generalized linear mixed models. There were significant condition effects for IL-6 and CRP. The sleep restriction/PBO condition showed higher values for IL-6 following 5 nights of restricted sleep compared to sleep restriction/ASA, while the sleep restriction/ASA condition did not differ from control sleep/PBO. For CRP, the sleep restriction/ASA condition had lower values following restricted sleep than sleep restriction/PBO and control sleep/PBO. Targeting inflammation pharmacologically via enhancing inflammatory resolution processes could provide a novel strategy to mitigate future disease risks in those undergoing periods of sleep restriction or prolonged sleep disturbances.

Projektbezogene Publikationen (Auswahl)

• 129 Greater NREM Sleep Rebound in Response to Experimental Sleep Disturbance Associated with Higher Inflammatory Resolution in Humans. Sleep, 44(Supplement_2), A52-A53.
  Engert, Larissa; Dubourdeau, Marc; Dang, Rammy; Mullington, Janet & Haack, Monika
  
• Non-REM sleep response during recovery sleep counteracts impaired inflammatory resolution due to sleep disturbance in healthy humans. Brain, Behavior, and Immunity, 98, 15.
  Engert, L.C.; Dubourdeau, M.; Dang, R.; Mullington, J.M. & Haack, M.
  
• 0287 Effects of Sleep Restriction and Recovery on the Capacity of Glucocorticoids to Inhibit Inflammatory Marker Expression in Human Monocytes. Sleep, 45(Supplement_1), A129-A130.
  Engert, Larissa; Eske, Annika; Buraks, Olivia; Dang, Rammy; Mullington, Janet & Haack, Monika
  
• Differential effects of an experimental model of prolonged sleep disturbance on inflammation in healthy females and males. PNAS Nexus, 1(1).
  Besedovsky, Luciana; Dang, Rammy; Engert, Larissa C.; Goldstein, Michael R.; Devine, Jaime K.; Bertisch, Suzanne M.; Mullington, Janet M.; Simpson, Norah & Haack, Monika
  
• Alterations of pain pathways by experimental sleep disturbances in humans: central pain-inhibitory, cyclooxygenase, and endocannabinoid pathways. SLEEP, 46(6).
  Haack, Monika; Engert, Larissa C.; Besedovsky, Luciana; Goldstein, Michael R.; Devine, Jaime K.; Dang, Rammy; Olia, Keeyon; Molina, Victoria; Bertisch, Suzanne M.; Sethna, Navil & Simpson, Norah
  
• Immune, neuroendocrine, and metabolic functions in insomnia disorder. Encyclopedia of Sleep and Circadian Rhythms, 113-122.
  Engert, Larissa C. & Haack, Monika
  
• Prolonged experimental sleep disturbance affects the inflammatory resolution pathways in healthy humans. Brain, Behavior, and Immunity, 113, 12-20.
  Engert, Larissa C.; Mullington, Janet M. & Haack, Monika