Chronic fatigue syndrome is a medically unexplained illness. One of the major hypotheses for its cause is immunological dysfunction, but no firm data exist to support the immunological hypothesis. We believe this is because prior researchers have ignored the role of cytokines in producing restful/restless sleep. Many CFS patients have disrupted sleep, and we posit that this occurs because of abnormalities in the pattern of sleep disrupting and sleep producing cytokines in some patients. We propose to measure sleep disrupting cytokines (i.e., IL-4 and IL-10) and sleep producing cytokines (IL-1beta and TNF-alpha) in CFS patients on their second night in the sleep laboratory (the first night being done to deal with the well known """"""""first night effect"""""""" and to eliminate patients with primary sleep disorders or an inability to sleep with instrumentation). In doing these studies, we are aware that there is no """"""""gold standard"""""""" to quantify cytokines, and so we will use three different approaches - ELISA of plasma levels, gene message in peripheral blood mononuclear cells (PBMC) and ELISPOT to assess PBMC responses to immunological probes. We will study women only because CFS is predominantly an illness of women, because we want to exclude subjects with primary sleep disorders that occur mostly in men, and because women have substantially higher levels of cytokines than men. We will exclude women with depression because depression alters sleep and cytokines. We will compare data of CFS patients to those of healthy controls who, on the blood sampling night, will have their total sleep time matched to CFS patients. Since some CFS patients sleep without disruption, we have developed a 2x2 design: CFS vs controls; and sleep disturbed vs normally sleeping. This design will allow us to determine whether CFS, the illness, rather than the disturbed sleep, a symptom of the illness, is responsible for altered cytokine patterns. We will repeat this entire protocol after subjects perform a maximal exercise test and during a night of total sleep deprivation. We anticipate that exercise, which is known to exacerbate CFS symptoms, will worsen an already dysregulated cytokine sleep network while sleep deprivation will also magnify the differences by increasing sleep-producing cytokines in CFS patients without sleep problems and in controls but not in patients with disrupted sleep.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI054478-04
Application #
7067678
Study Section
Special Emphasis Panel (ZRG1-CFS (01))
Program Officer
Esch, Thomas R
Project Start
2003-09-30
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$627,427
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Neurosciences
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
Pejovic, Slobodanka; Natelson, Benjamin H; Basta, Maria et al. (2015) Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the 'unitary' hypothesis. BMC Neurol 15:53
Togo, Fumiharu; Lange, Gudrun; Natelson, Benjamin H et al. (2015) Attention network test: assessment of cognitive function in chronic fatigue syndrome. J Neuropsychol 9:1-9
Togo, Fumiharu; Natelson, Benjamin H (2013) Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome. Auton Neurosci 176:85-90
Nakamura, Toru; Schwander, Stephan; Donnelly, Robert et al. (2013) Exercise and sleep deprivation do not change cytokine expression levels in patients with chronic fatigue syndrome. Clin Vaccine Immunol 20:1736-42
Biswal, Bharat; Kunwar, Pratap; Natelson, Benjamin H (2011) Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling. J Neurol Sci 301:9-11
Kishi, Akifumi; Natelson, Benjamin H; Togo, Fumiharu et al. (2011) Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia. Sleep 34:1551-60
Kishi, Akifumi; Natelson, Benjamin H; Togo, Fumiharu et al. (2010) Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia. Conf Proc IEEE Eng Med Biol Soc 2010:5391-4
Weaver, Shelley A; Janal, Malvin N; Aktan, Nadine et al. (2010) Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndrome patients with and without comorbid fibromyalgia. J Womens Health (Larchmt) 19:951-8
Togo, Fumiharu; Natelson, Benjamin H; Cherniack, Neil S et al. (2010) Sleep is not disrupted by exercise in patients with chronic fatigue syndromes. Med Sci Sports Exerc 42:16-22
Nakamura, Toru; Schwander, Stephan K; Donnelly, Robert et al. (2010) Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia. Clin Vaccine Immunol 17:582-7

Showing the most recent 10 out of 13 publications