Somnogenic cytokines and models concerning their effects on sleep.

All the sleep-promoting substances currently identified also have other biological activities. Despite years of effort, a single specific central nervous system sleep center has not been described. These observations led us to propose a biochemical model of a sleep activational system in which the effects of several sleep factors are integrated into a regulatory scheme. These sleep factors interact by altering the metabolism, production, or activity of each other and thereby result in multiple feedback loops. This web of interactions leads to sleep stability in that minor challenges to the system will not greatly alter sleep. The system, however, is responsive to strong perturbations, such as sleep deprivation and infectious disease. The sleep-promoting effects of cytokines and their interactions with prostaglandins and the neuroendocrine system are used to illustrate the functioning of a part of the sleep activational system under normal conditions and during infectious disease. Although the actions of individuals sleep factors are not specific to sleep, their interactions at various levels of the neuraxis can mediate a specific sleep response. Such a system would also be responsive to the autonomic and environmental parameters that alter sleep.