“We have discovered that sleep helps to regulate the production in
the bone marrow of inflammatory cells and the health of blood vessels
and that, conversely, sleep disruption breaks down control of
inflammatory cell production, leading to more inflammation and more
says Filip Swirski, PhD, of the MGH Center for Systems
Biology, senior author of the Nature paper.
“We also have
identified how a hormone in the brain known to control wakefulness
controls processes in the bone marrow and protects against
To investigate how insufficient sleep increases atherosclerosis,
Swirski’s team subjected mice genetically programmed to develop
atheroslcerosis to repeated interruptions of their sleep, similar to the
experience of someone constantly waking up because of noise or
While there were no changes in weight, cholesterol levels or
glucose tolerance in the sleep-deprived mice, compared to animals from
the same strain allowed to sleep normally, those subjected to sleep
fragmentation developed larger arterial plaques and had higher levels of
monocytes and neutrophils inflammatory cells that contribute to
atherosclerosis in their blood vessels.
Further experiments revealed that the sleep-deprived mice had a
nearly two-fold increase in the production in their bone marrow of stem
cells that give rise to white blood cells.
A hormone called hypocretin,
produced in the brain structure called the hypothalamus and known to
have a role in the regulation of sleep, was found to play an unexpected
role in controlling white blood cell production.
While normally produced
at high levels when animals including humans are awake,
hypocretin levels were significantly reduced in the sleep-deprived mice.
The MGH team found that hypocretin regulates production of white
blood cells through interaction with neutrophil progenitors in the bone
Neutrophils, they discovered, induce monocyte production through
release of a factor called CSF-1, and experiments with mice lacking the
gene for hypocretin revealed that the hormone controls CSF-1
expression, monocyte production and the development of arterial plaques.
In sleep-deprived animals, the drop in hypocretin led to increased
CSF-1 production by neutrophils, elevated monocyte production and
“This is a direct demonstration that hypocretin is also an important
inflammatory mediator,” says Swirski, an associate professor of
Radiology at Harvard Medical School. “We now need to study this pathway
in humans, explore additional mechanisms by which proper sleep maintains
vascular health and further explore this newly identified neuro-immune
Massachusetts General Hospital