Cytokines and normal sleep.
OBJECTIVE
Cytokines are mediators of immune system responses with multiple biologic actions on several target tissues. Over the past two decades, research has explored the interactions between cytokines and sleep mechanisms of the brain. This short review highlights selected findings that have advanced our understanding of the relation between cytokines and sleep.


RESULTS
A complex network of cytokines and their receptors exists in brain. Cytokines may either promote or inhibit sleep. Of cytokines studied thus far, evidence indicates that interleukin-1 and tumor necrosis factor play a role in the regulation of non-rapid eye movement sleep. Their sites of action for regulating such sleep likely include the hypothalamic preoptic area and the basal forebrain. Mechanisms of action include direct receptor-mediated effects on neurons and the synthesis and release of numerous transmitters, peptides, and hormones that lead to subsequent changes in sleep. Among others, the cascade of responses induced by cytokines that may lead to subsequent alterations in sleep includes alterations in nitric oxide synthesis and effects on neurohormonal systems such as growth hormone releasing hormone. The activation by cytokines of the hypothalamic-pituitary-adrenal axis also influences sleep. Studies suggest that there is a significant overlap between neurohormonal systems such as the somatotropic and hypothalamic-pituitary-adrenal axes and cytokines, particularly with regard to their effects on sleep-wake regulation.


CONCLUSIONS
There is increasing evidence of a role for cytokines in regulating spontaneous non-rapid eye movement sleep. The somatotropic hormonal system and hypothalamic-pituitary-adrenal axis mediate, in part, the effects of cytokines on sleep.
Kapsimalis
Fotis
F
Department of Pulmonology, Sleep Laboratory, Henry Dunant Hospital, Athens, Greece.
Richardson
Gary
G
Opp
Mark R
MR
Kryger
Meir
M
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone