scholarly journals Direct Evidence for Central Proinflammatory Mechanisms in Rats with Experimental Acute Liver Failure: Protective Effect of Hypothermia

2009 ◽  
Vol 29 (5) ◽  
pp. 944-952 ◽  
Author(s):  
Wenlei Jiang ◽  
Paul Desjardins ◽  
Roger F Butterworth
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Brain Edema ◽  
Proinflammatory Cytokines ◽  
Direct Evidence ◽  
Mild Hypothermia ◽  
Tnf Α ◽  
Factor Α ◽  
The Brain ◽  
Necrosis Factor

It has been proposed that proinflammatory mechanisms are involved in the pathogenesis of brain edema in acute liver failure (ALF). The aim of this study was to assess the contribution of cerebral inflammation to the neurologic complications of ALF and to assess the antiinflammatory effect of mild hypothermia. Upregulation of CD11b/c immunoreactivity, consistent with microglial activation, was observed in the brains of ALF rats at coma stages of encephalopathy. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNAs were increased two to threefold in the brains of ALF rats compared with that in sham-operated controls. The magnitude of increased expression of proinflammatory cytokines in the brain was correlated with the progression of encephalopathy and the onset of brain edema. Significant increases in IL-1β, IL-6, and TNF-α levels were also found in the sera and cerebrospinal fluid (CSF) of these animals. Mild hypothermia delayed the onset of encephalopathy, prevented brain edema, and concomitantly attenuated plasma, brain, and CSF proinflammatory cytokines. These results show that experimental ALF leads to increases in brain production of proinflammatory cytokines, and afford the first direct evidence that central inflammatory mechanisms play a role in the pathogenesis of the cerebral complications of ALF. Antiinflammatory agents could be beneficial in the management of these complications.

The Na–K–Cl cotransporter in the brain edema of acute liver failure

2011 ◽  
Vol 54 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Arumugam R. Jayakumar ◽  
Vanessa Valdes ◽  
Michael D. Norenberg
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Brain Edema ◽  
The Brain

The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands

2012 ◽  
Vol 303 (4) ◽  
pp. L327-L333 ◽  
Author(s):  
Nicholas Baniak ◽  
Xiaojie Luan ◽  
Amber Grunow ◽  
Terry E. Machen ◽  
Juan P. Ianowski
Keyword(s):  
Tumor Necrosis Factor ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 1Β ◽  
Tnf Α ◽  
Submucosal Glands ◽  
Factor Α ◽  
Airway Defense ◽  
Necrosis Factor

The airway is kept sterile by an efficient innate defense mechanism. The cornerstone of airway defense is mucus containing diverse antimicrobial factors that kill or inactivate pathogens. Most of the mucus in the upper airways is secreted by airway submucosal glands. In patients with cystic fibrosis (CF), airway defense fails and the lungs are colonized by bacteria, usually Pseudomonas aeruginosa . Accumulating evidence suggests that airway submucosal glands contribute to CF pathogenesis by failing to respond appropriately to inhalation of bacteria. However, the regulation of submucosal glands by the innate immune system remains poorly understood. We studied the response of submucosal glands to the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. These are released into the airway submucosa in response to infection with the bacterium P. aeruginosa and are elevated in CF airways. Stimulation with IL-1β and TNF-α increased submucosal gland secretion in a concentration-dependent manner with a maximal secretion rate of 240 ± 20 and 190 ± 40 pl/min, respectively. The half maximal effective concentrations were 11 and 20 ng/ml, respectively. The cytokine effect was dependent on cAMP but was independent of cGMP, nitric oxide, Ca2+, or p38 MAP kinase. Most importantly, IL-1β- and TNF-α-stimulated secretion was blocked by the CF transmembrane conductance regulator (CFTR) blocker, CFTRinh172 (100 μmol/l) but was not affected by the Ca2+-activated Cl− channel blocker, niflumic acid (1 μmol/l). The data suggest, that during bacterial infections and resulting release of proinflammatory cytokines, the glands are stimulated to secrete fluid, and this response is mediated by cAMP-activated CFTR, a process that would fail in patients with CF.

Involvement of brain cytokines in zymosan-induced febrile response

2014 ◽  
Vol 116 (9) ◽  
pp. 1220-1229 ◽  
Author(s):  
Amanda L. Bastos-Pereira ◽  
Daniel Fraga ◽  
Daniela Ott ◽  
Björn Simm ◽  
Jolanta Murgott ◽  
...  
Keyword(s):  
Time Course ◽  
Calcium Concentration ◽  
Febrile Response ◽  
Tnf Α ◽  
Heat Conservation ◽  
The Central Nervous System ◽  
Factor Α ◽  
The Brain ◽  
Circulating Levels ◽  
Necrosis Factor

This study compared the involvement of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) within the central nervous system (CNS) in the febrile response induced by zymosan (zym) and lipopolysaccharide (LPS). In addition, we investigated whether zym could activate important regions related to fever; namely, the vascular organ of the laminae terminalis (OVLT) and the median preoptic nucleus (MnPO). Intraperitoneal injection of zym (1, 3, and 10 mg/kg) induced a dose-related increase in core temperature. Zym (3 mg/kg) also reduced tail skin temperature, suggesting the activation of heat conservation mechanisms, as expected, during fever. LPS increased plasma levels of TNF-α measured at 1 h, IL-1β measured at 2 h, and IL-6 measured at 3 h after injection. Zym increased circulating levels of IL-6 but not those of TNF-α or IL-1β at the same time points. In addition, an intracerebroventricular injection of antibodies against TNF-α (2.5 μg) and IL-6 (10 μg) or the IL-1 receptor antagonist (160 ng) reduced the febrile response induced by zym and LPS. Zym (100 μg/ml) also increased intracellular calcium concentration in the OVLT and MnPO from rat primary neuroglial cultures and increased release of TNF-α and IL-6 into the supernatants of these cultures. Together, these results suggest that TNF-α, IL-1β, and IL-6 within the CNS participate in the febrile response induced by zym. However, the time course of release of these cytokines may be different from that of LPS. In addition, zym can directly activate the brain areas related to fever.

Diversity and Regulation of Astrocyte Neurotoxicity in Alzheimer's Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Sadayuki Hashioka ◽  
James G. McLarnon ◽  
Andis Klegeris
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Nuclear Imaging ◽  
Resonance Spectroscopy ◽  
Tnf Α ◽  
Factor Α ◽  
The Brain ◽  
Harmful Effects ◽  
Necrosis Factor

: Astrocytes contribute to brain development and homeostasis and support diverse functions of neurons. These cells also respond to the pathological processes in Alzheimer’s disease (AD). There is still considerable debate concerning the overall contribution of astrocytes to AD pathogenesis since both the protective and harmful effects of these cells on neuronal survival have been documented. This review focuses exclusively on the neurotoxic potential of astrocytes while acknowledging that these cells can contribute to neurodegeneration through other mechanisms, for example, by lowered neurotrophic support. We identify reactive oxygen and nitrogen species, tumor necrosis factor α (TNF-α), glutamate, and matrix metalloproteinase (MMP)-9 as molecules that can be directly toxic to neurons and are released by reactive astrocytes. There is also considerable evidence suggesting their involvement in AD pathogenesis. We further discuss the signaling molecules that trigger the neurotoxic response of astrocytes with a focus on human cells. We also highlight microglia, the immune cells of the brain, as critical regulators of astrocyte neurotoxicity. Nuclear imaging and magnetic resonance spectroscopy (MRS) could be used to confirm the contribution of astrocyte neurotoxicity to AD progression. The molecular mechanisms discussed in this review could be targeted in the development of novel therapies for AD.

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review

2018 ◽  
Vol 63 (6) ◽  
pp. 1654-1666 ◽  
Author(s):  
Beverley Kok ◽  
◽  
Erica L. W. Lester ◽  
William M. Lee ◽  
A. James Hanje ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Literature Review ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor
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