Chronic Interferon-Alpha Administration Disrupts Sleep Continuity and Depth in Patients with Hepatitis C: Association with Fatigue, Motor Slowing, and Increased Evening Cortisol

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Biological psychiatry (Impact Factor: 10.26). 11/2010; 68(10):942-9. DOI: 10.1016/j.biopsych.2010.04.019
Source: PubMed


Consequences of chronic exposure to cytokines of the innate immune system on sleep in humans and the association of cytokine-induced sleep alterations with behavior, motor performance, and cortisol secretion are unknown.
Thirty-one patients with hepatitis C without pre-existing sleep disorders underwent nighttime polysomnography, daytime multiple sleep latency testing, behavioral assessments, neuropsychological testing, and serial blood sampling at baseline and after ∼12 weeks of either treatment with the innate immune cytokine interferon (IFN)-alpha (n = 19) or no treatment (n = 12). Fatigue and sleepiness were assessed using the Multidimensional Fatigue Inventory and Epworth Sleepiness Scale.
Interferon-alpha administration led to significant increases in wake after sleep onset and significant decreases in stage 3/4 sleep and sleep efficiency. Rapid eye movement latency and stage 2 sleep were significantly increased during IFN-alpha treatment. Decreases in stage 3/4 sleep and increases in rapid eye movement latency were associated with increases in fatigue, whereas decreases in sleep efficiency were associated with reduced motor speed. Increased wake after sleep onset was associated with increased evening plasma cortisol. Despite IFN-alpha-induced increases in fatigue, daytime sleepiness did not increase. In fact, IFN-alpha-treated patients exhibited decreased propensity to fall asleep during daytime nap opportunities.
Chronic exposure to an innate immune cytokine reduced sleep continuity and depth and induced a sleep pattern consistent with insomnia and hyperarousal. These data suggest that innate immune cytokines may provide a mechanistic link between disorders associated with chronic inflammation, including medical and/or psychiatric illnesses and insomnia, which, in turn, is associated with fatigue, motor slowing, and altered cortisol.

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Available from: Charles L Raison, Jan 16, 2014
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    • "Hepatitis C patients have a high incidence of sleep disorders, depression, and anxiety during and after treatment with IFN-í µí»¼ and without treatment; thus, the effects on sleep appear to depend on the infection [71]. On the contrary, Raison showed that IFN-í µí»¼ therapy exacerbates these disorders—such patients had a significant decrease in sleep time in stages 3 and 4 and in sleep efficiency (total sleep time/time spent in bed × 100), whereas they experienced increased fatigue, took fewer naps during the day, and had greater plasma cortisol levels [72]. These data are indicators of stress in such patients and suggest that sleep disorders, depression, and anxiety result from deterioration of the emotional state and the immune response against the virus. "
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    • "Previous studies have linked high circulating levels of proinflammatory cytokines with co-occurring symptoms, including fatigue, depressive symptoms, sleep disturbances, and pain (Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002; Larson & Dunn, 2001). In addition, interferon gamma, a cytokine administered for the treatment of a variety of cancers as well as hepatitis C has also been found to induce fatigue (Raison et al., 2010; Sarkar, Jiang, Evon, Wahed, & Hoofnagle, 2012). Moreover, chronic low-grade inflammation is a key feature of obesity, a primary cause of the largest growing CLD subtype, NAFLD (World Gastroenterology Organization, 2012). "
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    • "There is a wide variety of adverse effects due to the use of interferon alpha 2a, including flu-like syndrome (unusual tiredness, fever, chills, muscle aches, and joint pain), injection site reaction (redness, pain at the site of injection), proneness to serious infections, new or worsening autoimmune disease 5– 7, myelosuppression 8, 9, depression, suicide, suicidal thoughts, and cardiovascular problems 10, 11 such as hypotension or hypertension, arrhythmia and myocardial infarction. Patients may also suffer from nausea, vomiting, loss of appetite, diarrhea, cough, dry mouth, dizziness, vertigo, sweating, itching, hair loss, fatigue, abdominal pain, constipation, sore throat, insomnia 12, anxiety and numbness. "
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