INFLUENCE OF ENDOTOXIN ON NOCTURNAL SLEEP IN HUMANS

Sleepiness is a common complaint during infectious diseases, but the i nteraction between sleep and host defense mechanisms has been poorly e xplored in humans. We therefore studied the effect of endotoxin, a maj or pathophysiological factor in gram-negative bacterial infections, on sleep and on parameters of the primary host response in men. In a sin gle-blind counterbalanced trial, 15 healthy volunteers received either placebo or Salmonella abortus equi endotoxin (0.4 ng/kg body wt) intr avenously on two separate occasions. Nocturnal sleep was recorded, and rectal temperature and the plasma levels of tumor necrosis factor-alp ha, interleukin-6, adrenocorticotropic hormone, and cortisol were moni tored for 12 h. Endotoxin reduced the relative amounts of wakefulness (P < 0.05) and rapid-eye-movement (REM) sleep (P < 0.05) and increased the relative amount of non-REM sleep (P < 0.01). Electroencephalogram delta power during non-REM sleep, as measured by spectral analysis, w as not altered by endotoxin. The endotoxin-induced changes in sleep st ructure were related temporally and quantitatively to the increases in rectal temperature and to the release of cytokines and neurohormones. It is concluded that cytokines and neurohormones mediate the effects of endotoxin upon sleep. The ensuing increase in non-REM sleep may be part of the adaptive host response to bacterial infections in humans.