Cytokine Regulation of Sleep Physiology

Sleep regulation emerges from a complex interplay between neural circuits and immune signalling; central to this interaction are cytokines—small protein mediators that convey immune status to the brain. Interleukin-1β and tumour necrosis factor-α act as endogenous somnogens, modulating non-rapid eye movement sleep homeostasis through effects on neuronal excitability, synaptic transmission and gene expression within sleep-regulatory centres. These cytokines oscillate in concert with circadian clocks, linking peripheral inflammation to alterations in sleep architecture. Inflammasome complexes such as NLRP3 integrate metabolic and pathogen-derived signals to control interleukin-1β maturation, further shaping sleep-wake dynamics during infection and sterile inflammation. Microglia, the brain’s resident immune cells, respond to peripheral and central immune cues, releasing cytokines that promote recovery sleep and support neuroprotective processes. Conversely, chronic or dysregulated cytokine production, as observed in autoimmune disease, obesity or ageing, leads to fragmented sleep, impaired cognitive function and heightened risk of metabolic and psychiatric comorbidity. Understanding the precise mechanisms by which cytokines influence neuronal networks offers potential for targeted interventions to restore healthy sleep in inflammatory disorders.

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Cytokine Regulation of Sleep Physiology publication trend

The graph below shows the total number of articles in cytokine regulation of sleep physiology across all publications each year (not limited to Nature Index journals).

Technical terms

Cytokine: A small, secreted protein that mediates communication between immune cells and influences neuronal or glial function.

Interleukin-1β: A pro-inflammatory cytokine that promotes non-rapid eye movement sleep and is activated by inflammasome complexes.

Tumour necrosis factor-α: A cytokine involved in systemic inflammation that modulates sleep intensity and promotes sleep under immune challenge.

Inflammasome: A multiprotein complex, such as NLRP3, that detects cellular stress or pathogens and triggers maturation of interleukin-1β.

Microglia: Resident immune cells of the central nervous system that produce cytokines and regulate synaptic and behavioural responses to inflammation.

Lipopolysaccharide (LPS): A component of bacterial cell walls used experimentally to induce systemic inflammation and stimulate cytokine-mediated sleep responses.

References

1. Neuroinflammation, Sleep, and Circadian Rhythms. Frontiers in Cellular and Infection Microbiology (2022).
2. Roles of Microglial Phagocytosis and Inflammatory Mediators in the Pathophysiology of Sleep Disorders. Frontiers in Cellular Neuroscience (2017).
3. Microglia Are Necessary to Regulate Sleep after an Immune Challenge. Biology (2022).
4. Lonicerae Japonicae Flos Extract Promotes Sleep in Sleep-Deprived and Lipopolysaccharide-Challenged Mice. Frontiers in Neuroscience (2022).