OBJECTIVE: Cytokines play an integral role in sleep/wake regulation. The objective of this study was to identify how total sleep deprivation affects cytokine levels.METHODS: Male C57BL/6 mice were subjected to 48 h of total sleep deprivation produced by brief rotation of activity wheels or 3 different controls: home cage, a sedentary wheel, or forced activity. In addition, the serum levels of cytokines were analyzed using a mouse magnetic bead-based multiplex immunoassay.RESULTS: The concentrations of some cytokines (fibroblast growth factor-basic [FGF-basic], leukemia inhibitory factor [LIF], and monokine induced by interferon-gamma [MIG]) decreased significantly after total sleep deprivation. However, other cytokines (macrophage colony-stimulating factor, macrophage inflammatory protein-2, platelet-derived growth factor-bb, vascular endothelial growth factor) did not show any significant difference. Serum corticosterone levels did not differ significantly among the groups.CONCLUSION: The biochemical mechanisms responsible for sleep regulation are very complex. These results suggest the involvement of 3 cytokines (FGF-basic, LIF, and MIG) in sleep/wake regulation.