Dose-dependent effects of endotoxin on human sleep

2000 ◽  
Vol 278 (4) ◽  
pp. R947-R955 ◽  
Author(s):  
Janet Mullington ◽  
Carsten Korth ◽  
Dirk M. Hermann ◽  
Armin Orth ◽  
Chris Galanos ◽  
...  

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 investigated the effects of three placebo-controlled doses of endotoxin on host response, including nocturnal sleep in healthy volunteers. Administered before nocturnal sleep onset, endotoxin dose dependently increased rectal temperature, heart rate, and the plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptors, interleukin (IL)-1 receptor antagonist, IL-6, and cortisol. The lowest dose reliably increased circulating levels of cytokines and soluble cytokine receptors, but it did not affect rectal temperature, heart rate, or cortisol. This subtle host defense activation increased deep NREM sleep amount, often referred to as slow-wave sleep (stages 3 and 4), and intensity (delta power). Conversely, the highest dose of endotoxin disrupted sleep. Whereas it is well established that the endocrine and thermoregulatory systems are very sensitive to endotoxin, this study shows that human sleep-wake behavior is even more sensitive to activation of host defense mechanisms.

1993 ◽  
Vol 264 (6) ◽  
pp. R1077-R1083 ◽  
Author(s):  
T. Pollmacher ◽  
W. Schreiber ◽  
S. Gudewill ◽  
H. Vedder ◽  
K. Fassbender ◽  
...  

Sleepiness is a common complaint during infectious diseases, but the interaction between sleep and host defense mechanisms has been poorly explored in humans. We therefore studied the effect of endotoxin, a major pathophysiological factor in gram-negative bacterial infections, on sleep and on parameters of the primary host response in men. In a single-blind counterbalanced trial, 15 healthy volunteers received either placebo or Salmonella abortus equi endotoxin (0.4 ng/kg body wt) intravenously on two separate occasions. Nocturnal sleep was recorded, and rectal temperature and the plasma levels of tumor necrosis factor-alpha, interleukin-6, adrenocorticotropic hormone, and cortisol were monitored 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, was not altered by endotoxin. The endotoxin-induced changes in sleep structure 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.


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6970
Author(s):  
Julianne M. Thornton ◽  
Kingsley Yin

Bacterial infection activates the innate immune system as part of the host’s defense against invading pathogens. Host response to bacterial pathogens includes leukocyte activation, inflammatory mediator release, phagocytosis, and killing of bacteria. An appropriate host response requires resolution. The resolution phase involves attenuation of neutrophil migration, neutrophil apoptosis, macrophage recruitment, increased phagocytosis, efferocytosis of apoptotic neutrophils, and tissue repair. Specialized Pro-resolving Mediators (SPMs) are bioactive fatty acids that were shown to be highly effective in promoting resolution of infectious inflammation and survival in several models of infection. In this review, we provide insight into the role of SPMs in active host defense mechanisms for bacterial clearance including a new mechanism of action in which an SPM acts directly to reduce bacterial virulence.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Marta M. Dimanico ◽  
Arndt-Lukas Klaassen ◽  
Jing Wang ◽  
Melanie Kaeser ◽  
Michael Harvey ◽  
...  

AbstractUnderstanding human sleep requires appropriate animal models. Sleep has been extensively studied in rodents, although rodent sleep differs substantially from human sleep. Here we investigate sleep in tree shrews, small diurnal mammals phylogenetically close to primates, and compare it to sleep in rats and humans using electrophysiological recordings from frontal cortex of each species. Tree shrews exhibited consolidated sleep, with a sleep bout duration parameter, τ, uncharacteristically high for a small mammal, and differing substantially from the sleep of rodents that is often punctuated by wakefulness. Two NREM sleep stages were observed in tree shrews: NREM, characterized by high delta waves and spindles, and an intermediate stage (IS-NREM) occurring on NREM to REM transitions and consisting of intermediate delta waves with concomitant theta-alpha activity. While IS-NREM activity was reliable in tree shrews, we could also detect it in human EEG data, on a subset of transitions. Finally, coupling events between sleep spindles and slow waves clustered near the beginning of the sleep period in tree shrews, paralleling humans, whereas they were more evenly distributed in rats. Our results suggest considerable homology of sleep structure between humans and tree shrews despite the large difference in body mass between these species.


SLEEP ◽  
2020 ◽  
Author(s):  
Shawn D X Kong ◽  
Camilla M Hoyos ◽  
Craig L Phillips ◽  
Andrew C McKinnon ◽  
Pinghsiu Lin ◽  
...  

Abstract Study Objectives Cardiovascular autonomic dysfunction, as measured by short-term diurnal heart rate variability (HRV), has been reported in older adults with mild cognitive impairment (MCI). However, it is unclear whether this impairment also exists during sleep in this group. We, therefore, compared overnight HRV during sleep in older adults with MCI and those with subjective cognitive impairment (SCI). Methods Older adults (n = 210) underwent overnight polysomnography. Eligible participants were characterized as multi-domain MCI or SCI. The multi-domain MCI group was comprised of amnestic and non-amnestic subtypes. Power spectral analysis of HRV was conducted on the overnight electrocardiogram during non-rapid eye movement (NREM), rapid eye movement (REM), N1, N2, N3 sleep stages, and wake periods. High-frequency HRV (HF-HRV) was employed as the primary measure to estimate parasympathetic function. Results The MCI group showed reduced HF-HRV during NREM sleep (p = 0.018), but not during wake or REM sleep (p &gt; 0.05) compared to the SCI group. Participants with aMCI compared to SCI had the most pronounced reduction in HF-HRV across all NREM sleep stages—N1, N2, and N3, but not during wake or REM sleep. The naMCI sub-group did not show any significant differences in HF-HRV during any sleep stage compared to SCI. Conclusions Our study showed that amnestic MCI participants had greater reductions in HF-HRV during NREM sleep, relative to those with SCI, suggesting potential vulnerability to sleep-related parasympathetic dysfunction. HF-HRV, especially during NREM sleep, may be an early biomarker for dementia detection.


1993 ◽  
Vol 75 (4) ◽  
pp. 1439-1443 ◽  
Author(s):  
J. M. Pinto ◽  
E. Garpestad ◽  
J. W. Weiss ◽  
D. M. Bergau ◽  
D. A. Kirby

To study the effects of airway obstruction (AWO) and arousal on coronary blood flow, mean arterial pressure (MAP), and heart rate, pigs were chronically instrumented with arterial catheters, Doppler flow probes on the left circumflex coronary artery, and electrodes for determination of sleep stages. A modified tracheostomy tube was placed in the trachea to obstruct the upper airway during sleep sessions. In control studies, during non-rapid-eye-movement (NREM) sleep, MAP was 84 +/- 2 mmHg before AWO and increased by 5 +/- 2 mmHg on arousal. MAP was lower during rapid-eye-movement (REM) sleep (62 +/- 2 mmHg), and the increase on arousal was fourfold greater (22 +/- 2 mmHg). Heart rate was similar in both sleep stages (NREM: 120 +/- 4 beats/min; REM: 124 +/- 5 beats/min) and increased significantly on arousal (NREM: 12 +/- 2 beats/min; REM: 18 +/- 1 beats/min). Coronary blood flow was similar during both stages (NREM: 43 +/- 4 ml/min; REM: 46 +/- 8 ml/min) and increased by 12–15% on arousal. Coronary vascular resistance index increased significantly by 24% on arousal from AWO during REM sleep. All increases and decreases were significant at P < 0.05. Receptor blockade studies were performed to assess alpha-adrenergic receptor involvement.


2020 ◽  
Vol 10 (9) ◽  
pp. 3336 ◽  
Author(s):  
Junichiro Hayano ◽  
Norihiro Ueda ◽  
Masaya Kisohara ◽  
Yutaka Yoshida ◽  
Haruhito Tanaka ◽  
...  

A variety of heart rate variability (HRV) indices have been reported to estimate sleep stages, but the associations are modest and lacking solid physiological basis. Non-REM (NREM) sleep is associated with increased regularity of respiratory frequency, which results in the concentration of high frequency (HF) HRV power into a narrow frequency range. Using this physiological feature, we developed a new HRV sleep index named Hsi to quantify the degree of HF power concentration. We analyzed 11,636 consecutive 5-min segments of electrocardiographic (ECG) signal of polysomnographic data in 141 subjects and calculated Hsi and conventional HRV indices for each segment. Hsi was greater during NREM (mean [SD], 75.1 [8.3]%) than wake (61.0 [10.3]%) and REM (62.0 [8.4]%) stages. Receiver-operating characteristic curve analysis revealed that Hsi discriminated NREM from wake and REM segments with an area under the curve of 0.86, which was greater than those of heart rate (0.642), peak HF power (0.75), low-to-high frequency ratio (0.77), and scaling exponent α (0.77). With a cutoff >70%, Hsi detected NREM segments with 77% sensitivity, 80% specificity, and a Cohen’s kappa coefficient of 0.57. Hsi may provide an accurate NREM sleep maker for ECG and pulse wave signals obtained from wearable sensors.


1975 ◽  
Vol 48 (5) ◽  
pp. 706-720 ◽  
Author(s):  
M. Schutte ◽  
R. DiCamelli ◽  
P. Murphy ◽  
M. Sadove ◽  
H. Gewurz

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 287
Author(s):  
Juan M. Vázquez-García ◽  
Gregorio Álvarez-Fuentes ◽  
Héctor O. Orozco-Gregorio ◽  
Juan C. García-López ◽  
Milagros González-Hernández ◽  
...  

We tested whether maternal energy supplementation during the last third of gestation improves birth weight, neonatal wellbeing, and mother–young bonding. Thirty-six pregnant French Alpine goats were randomly allocated among three nutritional treatments for the last third of pregnancy: (i) Control, fed alfalfa (T-0; n = 12); (ii) alfalfa + 150 g/head daily energy concentrate (T-150; n = 12); (iii) alfalfa + 300 g/head daily energy concentrate (T-300; n = 12). At birth, we collected progeny data on birth weight, birth type, sex, rectal temperature, heart rate, respiratory rate, time to standing, time to udder connection, and time to first feeding. For the dams, we collected data on the duration of labor, time to clean the progeny, and time to allow first suckling. At birth, body weight, rectal temperature, heart rate, and the respiratory rate did not differ among treatments (p > 0.05). In the dams, labor duration was not affected by the treatments (p > 0.05). The T-150 dams were faster to clean the newborn and allow first suckling (p < 0.05). The T-150 progeny were faster to stand and the T-300 progeny were faster to connect to the udder (p < 0.05). We conclude that energy supplementation of the dam during the last third of gestation does not affect the birth weight of the progeny, but enhances the mother–young bonding.


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