Dose-dependent effects of endotoxin on human sleep.

  title={Dose-dependent effects of endotoxin on human sleep.},
  author={Janet M Mullington and Carsten Korth and Dirk M. Hermann and A Orth and Chris Galanos and Florian Holsboer and Thomas Pollm{\"a}cher},
  journal={American journal of physiology. Regulatory, integrative and comparative physiology},
  volume={278 4},
The role of the central nervous system in the host response to infection and inflammation and modulation of these responses by the hypothalamic-pituitary-adrenal system are well established. In animals, activation of host defense mechanisms increases non-rapid eye movement (NREM) sleep amount and intensity, which, in turn, are thought to support host defense, or the body's ability to defend itself against challenges to its immune system. In humans, the evidence is conflicting. Therefore, we… 

Figures and Tables from this paper

Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans
The existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation, is suggested.
Experimental Immunomodulation, Sleep, and Sleepiness in Humans
Preliminary evidence from human studies suggesting that inflammatory cytokines such as TNF‐α not only mediate altered sleep‐wake behavior during infections, but in addition are involved in physiological sleep regulation and in hypnotic effects of established sedating drugs.
Brain-immune interactions in sleep.
Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans
Cytokines and sleep.
  • M. Opp
  • Biology, Psychology
    Sleep medicine reviews
  • 2005
Mediators of Inflammation and Their Interaction with Sleep
In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation, including TNF‐α, its soluble receptors, and IL‐6, present in the periphery and the CNS.
Low-dose endotoxemia and human neuropsychological functions


Influence of endotoxin on nocturnal sleep in humans.
It is concluded that cytokines and neurohormones mediate the effects of endotoxin upon sleep, and the ensuing increase in non-REM sleep may be part of the adaptive host response to bacterial infections in humans.
Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men.
The results underscore the importance of IL-6 in the cascade of cytokines for the neuroendocrine response during the acute phase reaction and appear to be involved in changes of sleep and behavior accompanying infection and inflammatory disorders.
Effects of granulocyte colony-stimulating factor on night sleep in humans.
It is concluded that G-CSF suppresses sleep intensity via increased circulating amounts of endogenous antagonists of IL-1β and TNF-α activity, suggesting that these cytokines are involved in human sleep regulation.
Tumor necrosis factor-beta induces sleep, fever, and anorexia.
The data suggest that TNF-beta may belong to the group of endogenous pyrogens/sleep factors, and the effects of T NF-beta on sleep-wake activity, brain temperature (Tbr), and food intake were unknown.
Influence of endotoxin on daytime sleep in humans
It is concluded that endotoxin administration in the morning to healthy volunteers, while activating the host defense to the same extent as a lower dose that has been reported to promote non-REM sleep when given in the evening, does not affect non- REM sleep.
Diurnal variations in the human host response to endotoxin.
Diurnal variations in the human susceptibility to endotoxin that may be due to a suppression of the biologic effects of TNF-alpha and IL-6 by endogenous glucocorticoids are demonstrated.
Interleukin 1-receptor antagonist blocks interleukin 1-induced sleep and fever.
Central administration of IL-1 to rabbits results in a characteristic febrile response and in increased non-rapid-eye-movement sleep (NREMS) and NREMS-promoting effects in rabbits.