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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    ABSTRACT: Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.
    Journal of Immunology Research 01/2015; 2015(4):1-14. DOI:10.1155/2015/678164 · 2.93 Impact Factor
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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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    ABSTRACT: Liver disease affects over 25 million people in the United States and, despite advances in medical management resulting in increased survival, a majority of these individuals report multiple co-occurring symptoms that severely impair functioning and quality of life. The purpose of this review is to (1) propose defining these co-occurring symptoms as a symptom cluster of chronic liver disease (CLD), (2) discuss putative underlying biological mechanisms related to CLD, including the liver-gut-brain axis and influence of the microbiome, and (3) discuss the implications for biobehavioral research in this patient population. Biobehavioral research focusing on the interrelated, and possibly synergistic, mechanisms of these symptoms may lead to the development and testing of targeted symptom management interventions for improving function and quality of life in this growing patient population.
    Biological Research for Nursing 07/2014; 17(2). DOI:10.1177/1099800414541541 · 1.43 Impact Factor
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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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    ABSTRACT: Purpose: To present a case who developed Bell’s palsy while using interferon alpha 2a for Behçet uveitis. Methods: A patient with Behçet disease presented with decreased vision in his right eye. Ophthalmic examination, fundus fluorescein angiography and optical coherence tomography were performed. After developing facial paralysis while on interferon therapy, the patient was referred to our neurology service for differential diagnosis and treatment. Results: Examination of right eye revealed panuveitis with branch retinal vein occlusion, so high dose steroids were prescribed. In three days there was no improvement in terms of vitreous inflammation and so steroids were replaced with interferon. At the seventh month, patient experienced a facial paralysis. After eliminating other causes, including viral infections, trauma, cold exposure and neurological evaluation with cranial MRI, the patient was diagnosed to have Bell’s palsy by a neurologist. Interferon was replaced with mycophenolate mofetil and the Bell’s palsy was treated with oral steroids. Conclusion: It is important to be alert to both common and rare complications while treating with interferon.
    F1000 Research 11/2013; 2:245. DOI:10.12688/f1000research.2-245.v1
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