EFFECTS
OF GRANULOCYTE COLONY-STIMULATING FACTOR ON SLEEP IN HUMANS
A. Schuld*, J.
Mulligton, D. Hinze-Selch, F. Holsboer, T. Pollm¬
cher. Max Planck Institute of
Psychiatry, Munich, Germany
The mechanisms underlying the
influence of host defense activation on complex brain
function are of major importance for psychoimmunology. In
animals, there is consistent evidence that altered sleep-wake
behavior during infection and inflammation is medicated by in
animatory cytokines such as IL-1b and TNF-a
. Human studies on the influence of endotoxin on sleep point
to the same direction. However, in addition to increase
circulating cytokine levels, endotoxin effects other
physiological systems that effect sleep such as neurendocrine
circuits or body temperature regulation. Therefore, it would
be important to know the effects of experimental strategies
on sleep that exclusively modulate cytokine networks. In
humans, G-CSF is known to increase the circulating levels of
TNF-a and endogenous antagonists of IL-1b
and TNF-a activity like IL-1Ra and soluble
TNF-receptors, but not to change body temperature or the
circulating levels of cortisol or growth hormone.
We injected 300 m
g of G-CSF subcutaneously to 10 healthy male volunteers at
2100 hours in a single-blind, placebo-controlled study
design. Blood samples for the determination of cytokine and
hormone plasma levels were taken intermittently, sleep was
recorded between 2300 and 0700 hours and analysed for sleep
stages and EEG spectral power. Besides robust increases in
leukocyte and granulocyte counts, G-CSF induced reliable
increases in the plasma levels of IL-1Ra and both soluble TNF
receptors within 2 hours after injection, followed by an
increase in TNF-a plasma levels some hours later. G-CSF
did neither influence body temperature nor the plasma levels
of cortisol and growth hormone, but it reduced slow wave
sleep amount and EEG delta power during the first two hours
of night sleep, when soluble TNF-receptors and IL-Ra, but not
TNF-a were elevated.
The findings support the
assumption that subtle changes in the systemic activity of
cytokines like IL-1b or TNF-a alter
CNS-function and sleep-wake behavior in particular.