Influence of endotoxin on nocturnal sleep in humans

1993 ◽  
Vol 264 (6) ◽  
pp. R1077-R1083 ◽  
Author(s):  
T. Pollmacher ◽  
W. Schreiber ◽  
S. Gudewill ◽  
H. Vedder ◽  
K. Fassbender ◽  
...  
Keyword(s):  
Rectal Temperature ◽  
Rem Sleep ◽  
Host Response ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Nocturnal Sleep ◽  
Primary Host ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Induced Changes

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.

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 ◽  
...  
Keyword(s):  
Heart Rate ◽  
Host Defense ◽  
Rectal Temperature ◽  
Host Response ◽  
Defense Mechanisms ◽  
Nrem Sleep ◽  
Sleep Stages ◽  
Nocturnal Sleep ◽  
Human Sleep ◽  
Sleep Amount

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.

scholarly journals Enterococcus faecalisDemonstrates Pathogenicity through Increased Attachment in anEx VivoPolymicrobial Pulpal Infection

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Wayne Nishio Ayre ◽  
Genevieve Melling ◽  
Camille Cuveillier ◽  
Madhan Natarajan ◽  
Jessica L. Roberts ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Host Response ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Streptococcus Anginosus ◽  
Cell Counts ◽  
Tnf Α ◽  
Factor Alpha ◽  
Infection Types

ABSTRACTThis study investigated the host response to a polymicrobial pulpal infection consisting ofStreptococcus anginosusandEnterococcus faecalis, bacteria commonly implicated in dental abscesses and endodontic failure, using a validatedex vivorat tooth model. Tooth slices were inoculated with planktonic cultures ofS. anginosusorE. faecalisalone or in coculture atS. anginosus/E. faecalisratios of 50:50 and 90:10. Attachment was semiquantified by measuring the area covered by fluorescently labeled bacteria. Host response was established by viable histological cell counts, and inflammatory response was measured using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. A significant reduction in cell viability was observed for single and polymicrobial infections, with no significant differences between infection types (∼2,000 cells/mm2for infected pulps compared to ∼4,000 cells/mm2for uninfected pulps).E. faecalisdemonstrated significantly higher levels of attachment (6.5%) thanS. anginosusalone (2.3%) and mixed-species infections (3.4% for 50:50 and 2.3% for 90:10), with a remarkable affinity for the pulpal vasculature. Infections withE. faecalisdemonstrated the greatest increase in tumor necrosis factor alpha (TNF-α) (47.1-fold forE. faecalis, 14.6-fold forS. anginosus, 60.1-fold for 50:50, and 25.0-fold for 90:10) and interleukin 1β (IL-1β) expression (54.8-fold forE. faecalis, 8.8-fold forS. anginosus, 54.5-fold for 50:50, and 39.9-fold for 90:10) compared to uninfected samples. Immunohistochemistry confirmed this, with the majority of inflammation localized to the pulpal vasculature and odontoblast regions. Interestingly,E. faecalissupernatant and heat-killedE. faecalistreatments were unable to induce the same inflammatory response, suggestingE. faecalispathogenicity in pulpitis is linked to its greater ability to attach to the pulpal vasculature.

scholarly journals Temperature-Induced Changes in Reperfused Stroke: Inflammatory and Thrombolytic Biomarkers

2020 ◽  
Vol 9 (7) ◽  
pp. 2108
Author(s):  
Paulo Ávila-Gómez ◽  
Pablo Hervella ◽  
Andrés Da Silva-Candal ◽  
María Pérez-Mato ◽  
Manuel Rodríguez-Yáñez ◽  
...  
Keyword(s):  
Body Temperature ◽  
Clot Lysis ◽  
Necrosis Factor Alpha ◽  
Poor Outcome ◽  
Tnf Α ◽  
Influence Of Temperature On ◽  
Factor Alpha ◽  
Higher Temperature ◽  
Poor Outcomes ◽  
Induced Changes

Although hyperthermia is associated with poor outcomes in ischaemic stroke (IS), some studies indicate that high body temperature may benefit reperfusion therapies. We assessed the association of temperature with effective reperfusion (defined as a reduction of ≥8 points in the National Institute of Health Stroke Scale (NIHSS) within the first 24 h) and poor outcome (modified Rankin Scale (mRS) > 2) in 875 retrospectively-included IS patients. We also studied the influence of temperature on thrombolytic (cellular fibronectin (cFn); matrix metalloproteinase 9 (MMP-9)) and inflammatory biomarkers (tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6)) and their relationship with effective reperfusion. Our results showed that a higher temperature at 24 but not 6 h after stroke was associated with failed reperfusion (OR: 0.373, p = 0.001), poor outcome (OR: 2.190, p = 0.005) and higher IL-6 levels (OR: 0.958, p < 0.0001). Temperature at 6 h was associated with higher MMP-9 levels (R = 0.697; p < 0.0001) and effective reperfusion, although this last association disappeared after adjusting for confounding factors (OR: 1.178, p = 0.166). Our results suggest that body temperature > 37.5 °C at 24 h, but not at 6 h after stroke, is correlated with reperfusion failure, poor clinical outcome, and infarct size. Mild hyperthermia (36.5–37.5 °C) in the first 6 h window might benefit drug reperfusion therapies by promoting clot lysis.

scholarly journals Febrile Core Temperature Is Essential for Optimal Host Defense in Bacterial Peritonitis

2000 ◽  
Vol 68 (3) ◽  
pp. 1265-1270 ◽  
Author(s):  
Qinqqi Jiang ◽  
Alan S. Cross ◽  
Ishwar S. Singh ◽  
T. Timothy Chen ◽  
Rose M. Viscardi ◽  
...  
Keyword(s):  
Core Temperature ◽  
Host Defense ◽  
Bacterial Infections ◽  
Bacterial Load ◽  
Cytokine Expression ◽  
Microbial Pathogens ◽  
Necrosis Factor Alpha ◽  
Bacterial Peritonitis ◽  
Tnf Α ◽  
Factor Alpha

ABSTRACT Fever, a nonspecific acute-phase response, has been associated with improved survival and shortened disease duration in infections, but the mechanisms of these beneficial responses are poorly understood. We previously reported that increasing core temperature of bacterial endotoxin (LPS)-challenged mice to the normal febrile range modified expression of tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and IL-6, three cytokines critical to mounting an initial defense against microbial pathogens, but survival was not improved in the warmer animals. We speculated that our inability to show a survival benefit of optimized cytokine expression in the warmer animals reflected our use of LPS, a nonreplicating agonist, rather than an infection with viable pathogens. The objective of this study was to determine if increasing murine core temperature altered cytokine expression and improved survival in an experimental bacterial peritonitis model. We showed that housing mice at 35.5°C rather than 23°C increased core temperature from 36.5 to 37.5°C to 39.2 to 39.7°C, suppressed plasma TNF-α expression for the initial 48 h, delayed gamma interferon expression, improved survival, and reduced the bacterial load in mice infected with Klebsiella pneumoniae peritonitis. We showed that the reduced bacterial load was not caused by a direct effect on bacterial proliferation and probably reflected enhanced host defense. These data suggest that the increase in core temperature that occurs during bacterial infections is essential for optimal antimicrobial host defense.

scholarly journals The Effects of Microtubule Stabilizing Drugs on Macrophage Immune-Mediated Endocytosis

2021 ◽  
Author(s):  
◽  
Praneta Joshi
Keyword(s):  
Bacterial Infections ◽  
Normal Function ◽  
Proliferating Cells ◽  
Necrosis Factor Alpha ◽  
Bacterial Killing ◽  
Microtubule Stabilization ◽  
Macrophage Activity ◽  
Cancer Chemotherapeutics ◽  
Immune Mediated ◽  
Factor Alpha

<p>Microtubule stabilizing drugs (MSD) bind and stabilize microtubules, thus inhibiting their normal function. MSD exhibit anti-mitotic effects which makes them attractive as cancer chemotherapeutics and much of existing research has focused on these effects in proliferating cells. In contrast, we are interested in assessing the effects of microtubule stabilization on non-proliferating cells, such as macrophages, to determine potential mitosis-independent actions of MSD on microtubule function. Thus, we investigated the effects of MSD on macrophage receptor-mediated endocytosis of low density lipoproteins (LDL) and found no significant effect on the ability of paclitaxel-treated macrophages to endocytose LDL. Alterations to macrophage phagocytic and killing efficiency due to treatment with paclitaxel, peloruside or docetaxel, as well as the recently discovered compounds, ixabepilone, mycothiazole, and zampanolide were investigated. Treatment with paclitaxel, peloruside or docetaxel did not significantly inhibit phagocytosis or killing of bacteria. Results from confocal microscopy suggest that paclitaxel alters phagocytic kinetics in macrophages. Respectively, zampanolide and mycothiazole significantly inhibited macrophage bactericidal and killing ability, while Ixabepilone enhanced bacterial killing. MSD treatment also altered production of tumor necrosis factor alpha (TNF-a) and nitric oxide (NO) during bacterial killing. Optimal activation of macrophages with IFN-y did not alter the effects of MSD. Taken together, these results suggest that MSD have multiple immunomodulatory effects unrelated to their anti-mitotic effects. The data suggests that during MSD treatment, macrophage activity maybe altered or impaired, thus modifying the ability of patients to fight off bacterial infections.</p>

scholarly journals The Coincidence of Necrotizing Enterocolitis and Rotavirus Infections and Potential Associations with Cytokines

2012 ◽  
Vol 23 (4) ◽  
pp. e103-e105 ◽  
Author(s):  
Efsun Sızmaz ◽  
Mehmet Satar ◽  
Ferda Özlü ◽  
Akgün Yaman ◽  
Hacer Yapıcıoğlu Yıldızdaş ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Necrotizing Enterocolitis ◽  
Tumour Necrosis ◽  
Bacterial Infections ◽  
Gastrointestinal Disease ◽  
Antigen Detection ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease in neonatal intensive care units. Although the pathogenesis of NEC remains unclear, evidence suggests that infections, especially bacterial infections, may play an important role. Viral infections may also result in NEC. Several outbreaks of NEC associated with rotaviruses have been described previously.OBJECTIVE: To investigate the association between rotavirus (RV) and serum interleukin (IL)-6 and IL-8 levels in infants with NEC.METHODS: RV infections were prospectively studied using antigen detection in the stools of 31 infants with NEC. Additionally, serum levels of IL-6, IL-8 and tumour necrosis factor-alpha were tested using micro-ELISA at 0 h and 48 h after diagnosis of NEC.RESULTS: Fecal specimens from 13 infants were positive, while fecal specimens from 18 infants were negative for RV according to antigen detection (RV+ and RV− groups, respectively). The mortality rate and the severity of NEC were not significantly different between the RV+ and RV− groups. IL-6 levels at 0 h and 48 h after diagnosis of NEC in RV+ infants were lower compared with RV− infants, while IL-8 levels were greater at 0 h and 48 h after diagnosis of NEC in RV+ infants compared with RV− infants.CONCLUSION: A high prevalence of RV infection in neonates with NEC was found. Decreased IL-6 levels and increased IL-8 and tumour necrosis factor-alpha levels in RV+ neonates with NEC suggests a role for RV in NEC.

scholarly journals Toll-Like Receptor 4-Positive Macrophages Protect Mice from Pasteurella pneumotropica-Induced Pneumonia

2003 ◽  
Vol 71 (2) ◽  
pp. 663-670 ◽  
Author(s):  
Marcia L. Hart ◽  
Derek A. Mosier ◽  
Stephen K. Chapes
Keyword(s):  
Bacterial Infections ◽  
Bone Marrow Cells ◽  
Early Recognition ◽  
Mouse Strains ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Inflammatory Protein ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT This study investigates Toll-like receptor 4 (TLR4)-positive macrophages in early recognition and clearance of pulmonary bacteria. TLR4 is a trans-membrane receptor that is the primary recognition molecule for lipopolysaccharide of gram-negative bacteria. The TLR4Lps-del mouse strains C57BL10/ScN (B10) and STOCK Abb tm1 TLR4 Lps-del Slc11a1s (B10 × C2D) are susceptible to pulmonary infections and develop pneumonia when naturally or experimentally infected by the opportunistic bacterium Pasteurella pneumotropica. Since these mice have the TLR4Lps-del genotype, we hypothesized that reconstitution of mice with TLR4-positive macrophages would provide resistance to this bacterium. A cultured macrophage cell line (C2D macrophages) and bone marrow cells from C2D mice were adoptively transferred to B10 and B10 × C2D mice by intraperitoneal injection. C2D macrophages increased B10 and B10 × C2D mouse resistance to P. pneumotropica. In C2D-recipient mice there was earlier transcription of tumor necrosis factor alpha and chemokines JE and macrophage inflammatory protein 2 (MIP-2) in the lungs of B10 and B10 × C2D mice, and there was earlier transcription of KC and MIP-1α in B10 × C2D mice. In addition, the course of inflammation following experimental Pasteurella challenge was altered in C2D recipients. C2D macrophages also protected B10 × C2D mice, which lack CD4+ T cells. These data indicate that macrophages are critical for pulmonary immunity and can provide host resistance to P. pneumotropica. This study indicates that TLR4-positive macrophages are important for early recognition and clearance of pulmonary bacterial infections.

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