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.