Tumor necrosis factor alpha in sleep regulation

Abstract

This review details tumor necrosis factor alpha (TNF) biology and its role in sleep, and describes how TNF medications influence sleep/wake activity. Substantial evidence from healthy young animals indicates acute enhancement or inhibition of endogenous brain TNF respectively promotes and inhibits sleep. In contrast, the role of TNF in sleep in most human studies involves pathological conditions associated with chronic elevations of systemic TNF and disrupted sleep. Normalization of TNF levels in such patients improves sleep. A few studies involving normal healthy humans and their TNF levels and sleep are consistent with the animal studies but are necessarily more limited in scope. TNF can act on established sleep regulatory circuits to promote sleep and on the cortex within small networks, such as cortical columns, to induce sleep-like states. TNF affects multiple synaptic functions, e.g., its role in synaptic scaling is firmly established. The TNF-plasticity actions, like its role in sleep, can be local network events suggesting that sleep and plasticity share biochemical regulatory mechanisms and thus may be inseparable from each other. We conclude that TNF is involved in sleep regulation acting within an extensive tightly orchestrated biochemical network to niche-adapt sleep in health and disease.

Longitudinal transcriptome-wide gene expression analysis of sleep deprivation treatment shows involvement of circadian genes and immune pathways

“…Given the enrichment observed in Tumor Necrosis Factor Alpha (TNF α ) and immune pathways, selected genes prominent in immune processes(25) were further examined ( Table S4 ).…”

“…Sleep and immunity are connected by anatomical and physiological bases (66). The role of cytokines in the brain is complex and remains to be fully understood; while a full discussion of their roles is beyond the scope of this work, Table S4 shows cytokines and substances which have been implicated in both immune and sleep regulatory processes (25). The present findings, observing upregulation after SD, support reports linking levels of pro-inflammatory cytokines to depression and suggesting involvement in disease pathogenesis (25, 67, 68).…”

“…One important clue to SD response may lie in the observed TNFα expression patterns. TNFα is a pro-inflammatory cytokine controlling expression of inflammatory genetic networks; in addition to many immune-related functions in the brain, it influences whole organism function, including sleep regulation (25, 60). After SD, patients had significantly decreased expression of TNF compared to controls (FDR q =0.01); upregulation was observed in controls and downregulation in patients.…”

“…While no systematic investigation of gene expression changes in depressed patients undergoing SD treatment has been conducted to date, the study of gene expression in major depressive disorder (MDD) has raised the idea that genes associated with MDD are enriched for inflammation and immune response pathways, which may be linked to the sleep disturbances observed in depression (23–25). Circadian rhythms are found in the majority of physiological processes and the immune system is no different, with alterations of these rhythms leading to disturbed immune responses (26).…”

Sueño y sistema inmune

“…34 El TNF actúa dentro de una amplia red bioquímica orquestada para adaptar al sueño en la salud y enfermedad. 36 Kapsimalis et al estudiaron la participación de las citocinas en la regulación espontánea del sueño NO MOR. 37 Los efectos de estas moléculas sobre el sueño están mediados por el sistema hormonal y el eje hipotálamo-pituitario-adrenal (HPA).…”