The role of interferon-alpha in the regulation of sleep

Interferon-alpha (IFN-alpha) exerts strong antiviral effects and was among the first cytokines suspected to contribute to alterations of sleep during infectious challenge. A short review of the relevant literature is provided . Administration of IFN-alpha in rabbits increased body temperature and; in parallel, slow wave sleep (SWS). These findings were taken to suggest a sl eep promoting effect of the cytokine. However, experiments in monkeys, alth ough indicating increased behavioral signs of fatigue, did not reveal chang es towards enhanced sleep after IFN-alpha. In cancer patients treated with high doses of IFN-alpha enhanced fatigue is commonly observed. We conducted a first study in healthy young men, evaluating the effects of IFN-alpha gi ven at a fairly low dose (1000 and 10,000IU/kg body weight, subcutaneously) on nocturnal sleep. The cytokine was administered subcutaneously at 19.00h prior to sleep. It distinctly reduced SWS during the early night and, at t he high dose, REM sleep across the entire night. Effects on sleep were acco mpanied by increased feelings of tiredness, increased pituitary-adrenal sec retory activity, increased growth hormone secretion and increased IL-6 plas ma concentrations. Body temperature remained almost unchanged. These result s support an acute disrupting effect of IFN-alpha on nocturnal sleep in hum ans. Similar disruptive effects have been observed in previous studies afte r administration of IL-6 in healthy humans. Together, the data support the view that enhanced release of proinflammatory cytokines in humans acutely i mpairs sleep. Given that the pattern of changes after IFN-alpha and also af ter IL-6 is in some of its essential features is reminiscent of the symptom s seen in depressed patients, a contribution of host defense mechanisms to this disease and associated sleep disruption should be taken into considera tion.