Cytokines and Sleep in CFS
Principal Investigator: Benjamin H Natelson, MD
This study is being conducted at our affiliated medical school, UMDNJ-New Jersey Medical School.
Background: 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 hypothesize 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-1b and TNF-a) 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).
Research Plan: 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 in plasma, gene message from peripheral blood mononuclear cells (PBMC) and ELISPOT to assess PBMC function 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 a day in which subjects perform a maximal exercise test and during a night of sleep deprivation.
Impact: We anticipate that exercise, which is known to exacerbate CFS symptoms, will worsen an already deregulated cytokine sleep network while sleep deprivation will alter cytokines in patients and controls similarly. Finding these results would confirm that cytokine abnormalities in CFS are related to the pathophysiology of the illness and not secondary consequences of poor sleep.