Sleep is essential for human health and represents an active state of unconsciousness that plays a critical role in restoring brain and body functions, as well as regulating the immune and cardiovascular systems.¹

The hypothesis that sleep and immune responses are linked was originally postulated by the Greek philosopher Aristotle, and is based on the observation that sickness is coupled with sleepiness behaviour, evolutionarily conserved to ensure host defence against infection or injury, and is supported by the evidence that inflammatory cytokines influence restorative sleep.² While the interplay between sleep and cardiovascular health has been already highlighted, the role played by immune mechanisms in their mutual interaction is still object of investigation. Of note, sleep disturbances have been associated with increased incidence of myocardial infarction (MI) in humans³ and leucocyte-driven atherosclerosis in experimental mice,⁴ suggesting the existence of a sleep-mediated neuro-immune axis that oversees cardiovascular health.

Healthy sleep controls the activity of the autonomic nervous system, one of the branches of the peripheral nervous system, which in turn is organized into the sympathetic and parasympathetic systems, responsible for the so-called ‘flight or fight’ and ‘rest and digest’ responses respectively, with a shift from sympathetic to parasympathetic outflow during the night. Inadequate sleep has been associated with increased sympathetic activity due to the loss of its nocturnal dip, leading to enhanced noradrenaline signalling through the β-adrenergic receptor that leads to pro-inflammatory responses.¹

Both sympathetic and parasympathetic systems play a determinant role in neuro-immuno-cardiovascular interactions. Whereas the heart is reached by both sympathetic and parasympathetic innervation, sympathetic chains are the dominant routes of neural control of immune organs.⁵ In this way, the brain communicates with the cardiovascular system by direct neural connections and indirect neural modulation of immune response, both critically involved in cardiovascular diseases.

A well-defined example of such neuro-immune interaction in cardiovascular pathology comes from studies in hypertensive mice where it was shown that stimuli like Angiotensin II and DOCA-salt, recruit the cholinergic reflex to increase the splenic sympathetic outflow and consequent T cell activation and egression that rise blood pressure.^6,7 The spleen, in addition, acts as a reservoir of monocyte whose release after angiotensin stimulation is triggered following MI and could contribute to cardiac damage.⁸

However, it remains unanswered whether the brain and heart reciprocally communicate to trigger neuro-immune activation and modulate sleep behaviour.