Transcript Does acute sleep deficiency affect markers of

Does acute sleep deficiency affect markers of
inflammatory resolution?
Monika Haack, Vrushank Bhatt, Moussa, Diolombi, Janet Mullington
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
Introduction
Various pro-inflammatory markers (e.g., IL-6, TNF, prostaglandins) robustly
respond to acute sleep deficiency, whether measured in urine, plasma, or
immune cells. It has been repeatedly shown that these markers do not return
to baseline after one or two nights of recovery sleep, suggesting that acute
sleep deficiency may disrupt the process of inflammatory resolution. This
poster introduces markers involved in resolution physiology, which has been
mainly studied in pre-clinical animal models, but may give promise to human
translation.
How does inflammation resolve?
The resolution of inflammation is an active, rather than passive process. The
newly discovered lipid mediators resolvins, maresins, lipoxins, and protectins
(Serhan et al., 2015) are part of this active biochemical program enabling the
resolution of inflammation and the return to baseline (Figure 1). These lipid
mediators derive from polyunsaturated fatty acids (PUFA), such as the
omega-3 PUFAs EPA and DHA, and can stimulate key cellular events
(counter-regulation of chemokines/cytokines, cessation of neutrophil tissue
infiltration, stimulation of macrophage-mediated actions etc.).
Preliminary data
Since proresolving markers have never been measured in the context of sleep, we first
investigated whether they are detectable in human plasma of healthy young participants, and
whether they respond to acute sleep deficiency followed by recovery sleep.
Results:
Methods:
Measurement of inflammatory
and proresolving markers in
blood
obtained
from
an
experimental model resembling
common sleep-wake behaviors
of restricting sleep during
week/work days and catching
up on sleep during weekend/
work-off days.
Figure 2: IL-6 positive
Measures:
monocytes increase upon
- IL-6 positive monocytes
repeated exposure to sleep
after stimulation with LPS,
restriction, without returning
to baseline levels after
quantified with flow cytointermittent recovery sleep
metry.
(N=14). The pro-resolving
- Proresolving markers delipid mediator resolvin E3
termined in plasma, using
decreases after 5 nights of
liquid chromatography-tanrestricted sleep, and further
dem mass spectrometry
decreases upon 2 nights of
(LC-MS-MS; Lipid Mediator
recovery sleep, suggesting
Metabololipidomics
Core,
that
sleep
deficiency
interferes with the active
Brigham
and
Women’s
process of inflammatory
Hospital Boston, Director
resolution (N=2).
Prof. Serhan).
Conclusion
Figure 1: Lipid-mediator biosynthesis in the resolution of acute inflammation that
enables the return to baseline. Adapted from Serhan et al., 2015.
-
First results from this work-in-progress suggest that acute sleep deficiency not only
affects proinflammatory markers, but also markers contributing to the active process of
inflammatory resolution.
The balance between proinflammatory and proresovling markers may be an area ripe for
exploring as an inflammatory-related biomarker of acute and chronic sleep deficiency.
References.
Support.
Serhan CN, Chiang N, Dalli J, Levy BD. Lipid Mediators in the Resolution of Inflammation. Cold
Spring Harbor Perspectives in Biology 2015;7.
NHLBI R01 HL105544 to MH; National Center of Research Resources UL1 TR001102 to the Harvard Clinical and
Translational Science Center.
[email protected]