Effects of Granulocyte Colony-Stimulating Factor on Sleep in Human



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.