Intracerebroventricular injection of TNF-α promotes sleep and is recovered in cervical lymph

Abstract

Recent studies have shown that the central nervous system (CNS) communicates with the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-α would not only influence the CNS by promoting sleep but also would be directly transmitted into the peripheral immune system. Five hundred nanograms of 125I-labeled TNF-α were injected into the lateral ventricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. 125I-TNF-α was measured in lymph nodes and control fat, skin, and muscle tissues 6 h postinjection. 125I-TNF-α was detected in the cervical lymphatics within the first 30 min and peaked within 2-3 h. 125I-TNF-α counts were elevated in the nodes of the head and neck region. Polysomnographic recordings of four animals showed that TNF-α induced a significant increase in slow-wave sleep at postinjection hours 4 and 5, CNS TNF-α and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and peripheral immune functions.