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

Recent studies have shown that the central nervous system (CNS) communicate s with the periphery by the drainage of cerebrospinal fluid and brain inter stitial fluid into blood and lymph, me hypothesized that tumor necrosis fac tor (TNF)-alpha would not only influence the CNS by promoting sleep but als o would be directly transmitted into the peripheral immune system. Five hun dred nanograms of I-125-labeled TNF-alpha were injected into the lateral ve ntricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. I-125-TNF-alpha was measured i n lymph nodes and control fat, skin, and muscle tissues 6 h postinjection. I-125-TNF-alpha was detected in the cervical lymphatics within the first 30 min and peaked within 2-3 h. I-125-TNF-alpha counts were elevated in the n odes of the head and neck region. Polysomnographic recordings of four anima ls showed that TNF-alpha induced a significant increase in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-alpha and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and perip heral immune functions.