ABSTRACT
The anti-inflammatory cytokines interleukin (IL)-4 and IL-10 inhibit production of IL-1 and tumor necrosis factor (TNF) and both inhibit sleep. Several other cytokines have been shown to be somnogenic; the list includes interferon-a, acidic fibroblast growth factor, interleukin-2, nerve growth factor and epidermal growth factor. Histaminergic neurons may also be involved in cytokine sleep mechanisms. Neurotoxic lesions of histaminergic neurons decrease TNF-alpha in the posterior hypothalamus while enhancing TNF production in the hippocampus. TNFα and IL-1beta affect many other neurotransmitter systems. For example, IL-1 activates dopaminergic, adrenergic, cholinergic, and serotinergic systems. The coordination of sleep between neuronal groups is brought about by the neural networks previously implicated in sleep regulation. Sleep can thus be envisioned to be regulated by “bottom-up” mechanisms rather than by “top down” state imposition by sleep centers or circuits.
