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Influence of host defense activation on sleep in humans

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Despite considerable progress in our understanding of the
phenomenology of sleep and wakefulness, their regulation and
peculiar functions are poorly understood. Recent animal
research has revealed considerable evidence for interactions
between host defense and sleep. Therefore, it has been
hypothesized that host response mediators, mainly cytokines
like interleukin-1 (IL-1), are involved in physiological sleep
regulation.

Furthermore, it has been suggested that sleep, and
non rapid eye movement (NREM) sleep in particular, has an
immuno-supportive function. In humans, sleep-host defense
interactions are just starting to be understood. There is
quite good evidence that some viral diseases cause excessive
sleepiness. Other infectious diseases induce, however, serious
disturbances of the distribution of sleep and wakefulness
rather than excessive sleep. In addition, some disorders with
excessive sleep, daytime fatigue or disturbed night sleep as
prominent symptoms are thought to involve, at least in part,
immuno-pathophysiological mechanisms.

Experimental settings have only recently been used to
elucidate host defense-sleep interactions in humans. The
effects of endotoxin, a cell-wall lipopolysaccharide of
gram-negative bacteria, on sleep have been tested in
different settings in healthy volunteers. Endotoxin transiently
suppresses rapid eye movement (REM) sleep independently
of the time of the day of administration. Only low doses,
given in the evening, promote NREM sleep.

Electorencephalogram (EEG) power in higher frequency bands is
enhanced during NREM sleep, whereas delta activity is not
affected. In rats and rabbits, on the other hand, the effects
of endotoxin and of the mediators of its activity on REM sleep
are variable. Enhanced NREM sleep is a common finding and most
pronounced during the active part of the nycthemeron and, in
general, EEG delta activity is augmented.

In view of thesespecies differences, hypotheses regarding the
underlying mechanisms and the biological significance of host
defense-sleep interactions, primarily derived from the results
of animal studies, may not entirely fit human physiology. They
should therefore be re-evaluated and probably modified,
through the use of additional experimental approaches in
humans.

Pollmacher T, Mullington J, Korth C, Hinze-Selch D

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