Tnf Il1p

In animals, increases in the intracerebral or plasma levels of either TNF on IL-1P result in an increase in SWS duration, whereas decreases in the intracerebral levels of TNF or IL-1P inhibit SWS. The injection of cytokine into the right or left lobe affects changes in SWS and fever, demonstrating that these responses are independent of each other. Antagonizing either of these cytokines (by pretreatment with antibodies) leads to decreased sleep, indicating that they have a role in the physiological regulation of sleep. Interestingly, each of these cytokines influences the effect the other has on sleep. Pretreatment with a fragment of the receptor for IL-1P (type 1 IL-1R, IL-1R1) attenuates TNF-induced SWS enhancement, and TNF antagonists inhibit IL-1P-induced increases in SWS duration. TNF and IL-1P both stimulate the transcriptional activity of nuclear factor-kB (NF-kB) and enhance sleep. Factors that inhibit NF-kB activation, such as IL-4, IL-10 and inhibitor of NF-kB (IkB), inhibit sleep. NF-kB itself promotes the production on TNF and IL-1P, forming a positive-feedback loop, possibly to promote the homeostatic drive for sleep. This is supported by the finding that sleep deprivation causes increased levels of NF-kB in the central nervous system (Bryant, Trinder, and Curtis 2004).

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