CYTOKINES IN SLEEP REGULATION

The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infe ction and in the physiological regulation of sleep. We hypothesize tha t many cytokines, their cellular receptors, soluble receptors, and end ogenous antagonists are involved in physiological sleep regulation. Th e expressions of some cytokines are greatly amplified by microbial cha llenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at differen t times during the course of the infectious process result from dynami c changes in various cytokines that occur during the host's response t o infectious challenge. Removal of any one somnogenic cytokine inhibit s normal sleep, alters the cytokine network by changing the cytokine m ix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/ autocrine fashion and is responsive to neuronal use. Finally, cytokine s elicit their somnogenic actions via endocrine and neurotransmitter s ystems as well as having direct effects on neurons and glia. Evidence in support of these postulates is reviewed in this essay.