| Program : Biomedical Research and Countermeasures | Ground Research | ||||
| Element : Behavior and Performance | |||||
Sustained Partial Sleep Deprivation: Effects on Immune Modulation and Growth Factors |
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| Principal Investigator: | |||||
Janet M. Mullington, Ph.D. Department of Neurology KS 433 Harvard Medical School Beth Israel Deaconess Medical Center 330 Brookline Avenue Boston, MA 02215 |
Phone: (617) 667-0434 Email: jmulling@bidmc.Harvard.edu Fax: (617) 975-5506 Congressional District: MA-8 | ||||
| Co-Investigator(s): | |||||
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| Monitoring Center: NSBRI | Solicitation: NSBRI | ||||
| Initial Funding Date: | Expiration: | ||||
| Students Funded Under Research: | Post-Doctoral Associates: 0 | ||||
| Task Description: | |||||
| The vulnerability to human performance errors or medical emergencies is greatest in space where there are real limits to the availability or effectiveness of ground based assistance. The National Space Biomedical Research Institute's Human Performance Factors, Sleep and Chronobiology Team (Dr. Charles Czeisler, Leader) has approached the problems associated with performance failure from the perspective of optimizing performance capacity. Two conditions from one of the team projects, "Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight" (David Dinges, project PI), are being used to investigate 24-hour neuroendocrine and neuroimmune profiles, growth factors, and immune function. During space flight, muscle mass and bone density are reduced due to loss of gravity. Since >70% of growth hormone (GH) is secreted at night in normal adults, we hypothesized that the chronic sleep restriction to 4 hours per night would reduce GH levels as measured in the periphery. In this synergy project, in collaboration with Dr. Robert Schwartz, leader of the Muscle Alterations and Atrophy team, we are measuring insulin-like growth factor-I (IGF-I) in peripheral circulation to test the hypothesis that it will also be reduced by chronic sleep restriction. Medical complications, which would not pose a serious problem on earth, may be disastrous if they emerged in space. The Hematology, Immunology and Infection Team (Dr. William Shearer, Leader) is addressing issues of immune regulation in space, to alterations in function produced by weightlessness and the stresses associated with space flight and living in confined spaces. In long- term space flight, the issue of immune suppression and possible reactivation of latent viruses are risks that cannot be prevented by preflight quarantine. The possibility of reactivation of latent viruses is a serious potential hazard for the success of long-term space missions where confined conditions increase the possibility of transmitting disease (Janet Butel, NSBRI project PI, Immune Function and Reactivation of Latent Viruses). In addition to stress modulation of immune function, recent research suggests that sleep is also involved. While we all have the common experience of being sleepy when suffering from infection, and being susceptible to infection when not getting enough sleep, the mechanisms involved in this process are not understood, and until recently, have been largely overlooked. We believe that the immune function changes seen in spaceflight may also be related to the cumulative effects of sleep loss. This project synergizes the aims of the Human Performance Factors, Sleep and Chronobiology, the Muscle Alterations and Atrophy, and the Hematology, Immunology and Infection teams through the investigation of the effects of sustained sleep restriction to 4 hours per night (for 10 days) on growth factors, neuroendocrine and neuroimmune parameters. We are also investigating the effects of sleep loss on the reactivation of latent viruses. This work will be the first to examine the effects of chronic partial sleep loss on the reactivation of latent viruses and on cytokine profiles and on neuroendocrine parameters. | |||||
| Ten subjects have completed participation in a 14-day ground-based study, randomly assigned to either an 8.2 hr per night control condition or a 4.2 hr per night partial sleep deprivation condition, for 10 nights following baseline adaptation of 8.2 hr of sleep per night for 2 nights. Recovery sleep was permitted for 2 nights following the experimental period. On the first baseline and 9th night in the experimental portion of the protocol, subjects wore an indwelling forearm catheter, attached to a blood collection pump. Integrated blood samples were gathered from the pumps by nurses, at 15 min intervals throughout the following 25 hrs. Additional blood samples were drawn at baseline and on the 9th day of partial sleep deprivation for the measurement of white blood cells and other routine parameters and for the assessment of latent viruses. Urine specimens were also collected for the purposes of detecting the shedding of latent viruses. We have analyzed blood samples for hormones, cytokines and blood cell parameters, and both blood and urine samples for latent viruses. Lymphocyte and monocyte numbers rose from baseline levels as compared with after 9 nights of partial sleep deprivation. While these changes were small, they were evident in 4 of 5 subjects. All subjects had increased platelet numbers after 10 nights of partial sleep deprivation. The increases in lymphocyte and monocyte numbers were consistent with patterns that have been reported in response to 64 hours of total sleep deprivation (by David Dinges (Co-I) and colleagues). In addition to cortisol, melatonin and growth hormone, measured in the larger study, we measured insulin-like growth factor (IGF-I). We found an increase in this growth factor during sustained partial sleep deprivation. Cytokines involved in the regulation of inflammatory processes were measured, including TNF-alpha, TNF-receptors p55 and p75, IL-1 receptor antagonist and IL-10. IL-2, a major T-cell regulating cytokine, whose production has previously shown to be altered by acute total sleep loss, was also measured. The only cytokine altered by the partial sleep deprivation experimental condition was IL-1 receptor antagonist, which was elevated by day 9 of sleeping 4 hrs per night. No change was found in any other cytokines measured. Peripheral blood mononeuclear cells were extracted from blood samples and tested (DNA analysis using PCR techniques) for the presence of BK virus, JC virus, and SV40 virus. DNA extracted from sedimented urine pellets derived from urine and tested for the presence of BK virus, JC virus, and SV40. The only latent virus detected was in the urine of one subject (in the partial sleep deprivation condition) positive for JCV at both baseline and following 10 nights of PSD, and no other viruses were detected in blood or urine. Analyses of blood and urine for presence of Epstein-Barr virus are underway. While the 4.2 hr sleep per night experimental group in this study is of small numbers (4 for some parameters and 5 for others), results of this synergy project suggest that prolonged partial sleep deprivation alters neuroendocrine and neuroimmune parameters. More subjects will be studied in future partial sleep deprivation protocols to confirm and extend these exciting preliminary data. | |||||
| The results of this study will help determine the role of sleep in neuroendocrine and neuroimmune regulation. These results will address the effects of sleep loss of a kind often experienced during sustained and emergency operations (chronic sleep reduction rather than acute total sleep deprivation) on neuroendocrine and neuroimmune parameters that play an important role in general homeostatic physiology and on the reactivation of latent viruses that may be implicated in the development of a variety of cancers. The findings of this study will therefore be important for the development of countermeasures for illness prevention in long-term space travel as well as on earth. | |||||
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