Sleep, cytokines and immune function.

Bi-directional communication pathways exist between the brain and the cytokine-immune-endocrine systems. The hypothalamic-pituitary axis, the efferent neuronal hypothalamus-autonomic nervous system axis, and the direct drainage of macromolecules from the brain into the blood and the lymphatic system provide a network by which the sleeping/waking brain influence bodily functions. Similarly, changes in cytokine levels in the periphery modulate the central nervous system either directly or via the vagal nerve and influence the sleeping/waking brain. In humans, circadian nocturnal sleep-daytime wakefulness is associated with changes in peripheral cytokines, cellular immune functions, and endocrines. Progesterone levels influence sleep and cellular immune functions during the menstrual cycle. The interaction between the circadian sleeping/waking brain and the cytokine-immune-endocrine system are integral to preserving homeostasis. Disorganization or loss of sleep disrupts the harmonious integration of the circadian cytokine-immune-endocrine system. However, the mechanisms of circadian sleep/wakefulness-related cytokine-immune-endocrine functions in host defence against disease remain to be determined.