Humoral sleep regulation; interleukin-1 and tumor necrosis factor.

Two substances, the cytokines interleukin-1 beta (IL1β) and tumor necrosis factor alpha (TNFα), known for their many physiological roles, for example, cognition, synaptic plasticity, and immune function, are also well characterized in their actions of sleep regulation. These substances promote non-rapid eye movement sleep and can induce symptoms associated with sleep loss such as sleepiness, fatigue, and poor cognition. IL1β and TNFα are released from glia in response to extracellular ATP. They bind to their receptors on neurons resulting in neuromodulator and neurotransmitter receptor up/downregulation (e.g., adenosine and glutamate receptors) leading to altered neuronal excitability and function, that is, a state change in the local network. Synchronization of state between local networks leads to emergent whole brain oscillations, such as sleep/wake cycles.