INFLUENCE OF HOST-DEFENSE ACTIVATION ON SLEEP IN HUMANS

Despite considerable progress in our understanding of the phenomenolog y of sleep and wakefulness, their regulation and peculiar functions ar e poorly understood. Recent animal research has revealed considerable evidence for interactions between host defense and sleep. Therefore, i t has been hypothesized that host response mediators, mainly cytokines like interleukin-1 (IL-1), are involved in physiological sleep regula tion. Furthermore, it has been suggested that sleep, and non rapid eye movement (NREM) sleep in particular, has an immunosupportive function . In humans, sleep-host defense interactions are just starting to be u nderstood. There is quite good evidence that some viral diseases cause excessive sleepiness. Other infectious diseases induce, however, seri ous disturbances of the distribution of sleep and wakefulness rather t han excessive sleep. In addition, some disorders with excessive sleep, daytime fatigue or disturbed night sleep as prominent symptoms are th ought to involve, at least in part, immuno-pathophysiological mechanis ms. Experimental settings have only recently been used to elucidate ho st defense-sleep interactions in humans. The effects of endotoxin, a c ell-wall lipopolysaccharide of gramnegative bacteria, on sleep have be en tested in different settings in healthy volunteers. Endotoxin trans iently suppresses rapid eye movement (REM) sleep independently of the time of the day of administration. Only low doses, given in the evenin g, promote NREM sleep. Electorencephalogram (EEG) power in higher freq uency bands is enhanced during NREM sleep, whereas delta activity is n ot affected. In rats and rabbits, on the other hand, the effects of en dotoxin and of the mediators of its activity on REM sleep are variable . Enhanced NREM sleep is a common finding and most pronounced during t he active part of the nycthemeron and, in general, EEG delta activity is augmented. In view of these species differences, hypotheses regardi ng the underlying mechanisms and the biological significance of host d efense-sleep interactions, primarily derived from the results of anima l studies, may not entirely fit human physiology. They should therefor e be re-evaluated and probably modified, through the use of additional experimental approaches in humans.