Hepatic Encephalopathy Aggravated by Systemic Inflammation

2019 ◽  
Vol 37 (6) ◽  
pp. 509-517 ◽  
Author(s):  
Elina Manzhalii ◽  
Oleksandr Virchenko ◽  
Tetyana Falalyeyeva ◽  
Valentyna Moiseienko ◽  
Taras Nykula ◽  
...  

Background: The pathogenesis of hepatic encephalopathy (HE) is only partially understood. Beside ammonia accumulation in brain, a proinflammatory component has been suggested as precipitating event. Objectives: To evaluate the role of cytokines in cirrhosis for development of HE. Methods: Pro- and anti-inflammatory cytokine profiles were determined in rats with CCL4-induced cirrhosis and HE as well as in patients with cirrhosis either due to metabolic disorders or chronic hepatitis C virus (HCV) with various grades of concomitant HE and depression. Results: In the rat model and human cirrhosis a proinflammatory cytokine pattern (elevation of interferon gamma, interleukin [IL]-1β, IL-6) was registered which in humans correlated to the degree of HE and depression. The most prominent elevation of proinflammatory cytokines was observed in chronic HCV as an additional inflammatory stimulus. In all cases of cirrhosis a comparable background activation of anti-inflammatory cytokines (e.g., IL-4) was detected which was interpreted as a physiologic counterbalance mechanism. Conclusions: The degree of HE and depression correlated with a proinflammatory cytokine pattern. It suggests that beside ammonia elevation, inflammatory cytokines determine occurrence and severity of hepatic encephalopathies. Thus, it can be defined a preferential therapeutic target.

2007 ◽  
Vol 2007 ◽  
pp. 1-6 ◽  
Author(s):  
Levent Sutcigil ◽  
Cagatay Oktenli ◽  
Ugur Musabak ◽  
Ali Bozkurt ◽  
Adnan Cansever ◽  
...  

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-α, TGF-β1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-α) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-β1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-β1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.


Brain ◽  
2018 ◽  
Vol 141 (12) ◽  
pp. 3343-3360 ◽  
Author(s):  
Mélanie Morin-Brureau ◽  
Giampaolo Milior ◽  
Juliette Royer ◽  
Farah Chali ◽  
Caroline Le Duigou ◽  
...  

Using transcriptomics, anatomical studies, imaging and ELISA, Morin-Brureau et al. examine microglia in patients with temporal lobe epilepsies. In highly sclerotic regions such as CA1, the anti-inflammatory cytokine IL-10 regulates microglial phenotype. Seizures induce a transient microglial phenotype associated with secretion of inflammatory cytokines including human CXCL8.


2015 ◽  
Vol 11 (4) ◽  
pp. 1169-1173 ◽  
Author(s):  
Mahdi Hasanzadeh Daloee ◽  
Amir Avan ◽  
Seyed Reza Mirhafez ◽  
Elahe Kavousi ◽  
Mehdi Hasanian-Mehr ◽  
...  

Inflammation plays a key role in the initiation, progression, and clinical manifestation of atherosclerosis. Cigarette smoking is a risk factor for atherosclerosis and cardiovascular disease. The aim of the current study was to investigate the serum concentrations of 12 cytokines and growth factors (EGF, INF-γ, IL-1α/-1β/-2/-4/-6/-8/-10, MCP-1, TNF-α, and VEGF) in an Iranian population, including 192 smokers, comparing these values with concentrations in nonsmokers. One hundred and ninety-two cases were enrolled from the Mashhad University of Medical Sciences. Of these cases, 82 were cigarette smokers and 110 were nonsmokers. Sex and age were matched for the two groups. The serum concentration of 12 cytokines and growth factors were determined using EV-3513-cytokine-biochip arrays, by competitive chemiluminescence immunoassays. The level of serum MCP-1 was significantly ( p < .001) lower in the female group of cigarette smokers (mean = 88.1 dL/ng), compared with nonsmokers (mean = 155.6 dL/ng). There were no significant differences for the other cytokines and growth factors between the groups. Our finding demonstrate the association of MCP-1 with cigarette smoking, supporting further studies in larger population on evaluating the role of cigarette smoking on pro-/anti-inflammatory cytokines.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hector A Cabrera-Fuentes ◽  
Klaus T Preissner ◽  
William A Boisvert

As an important component of atherosclerosis, monocytes/macrophages respond to external stimuli with rapid changes in their expression of many inflammation-related genes to undergo polarization towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. Although sialoadhesin (Sn), also known as SIGLEC-1 or CD169, is a transmembrane protein receptor expressed on monocytes and macrophages whether it has a role in macrophage polarization and ultimately, macrophage-driven atherogenesis, has not been investigated. We have previously shown that, independently of Toll-like receptor signaling, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system by inducing cytokine mobilization. In the current study, recombinant mouse macrophage CSF[[Unable to Display Character: &#8211;]]driven bone marrow-derived macrophage (BMDM) differentiation was found to be skewed towards the M1 phenotype by exposure of cells to eRNA. This resulted in up-regulation of inflammatory markers, whereas anti-inflammatory genes were significantly down-regulated by eRNA. Interestingly, eRNA was released from BMDM under hypoxia and induced TNF-α liberation by activating TNF-α converting enzyme (TACE) to provoke inflammation. Conversely, TNF-α promoted eRNA release, especially under hypoxia, feeding a vicious cycle of cell damage. Administration of RNase1 or TAPI (a TACE-inhibitor) prevented the production of inflammatory mediators. Murine BMDM isolated from mice deficient in sialoadhesin had the opposite reaction to eRNA treatment with a prominent down-regulation of pro-inflammatory cytokines/M1 phenotype markers, while anti-inflammatory cytokines/M2 phenotype markers were significantly raised. In keeping with the proposed role of eRNA as a pro-inflammatory “alarm signal”, these data further shed light on the role of eRNA in macrophage function in the context of chronic inflammatory diseases such as atherosclerosis. The identification of sialoadhesin as putative eRNA recognition site on macrophages may allow further investigation of the underlying mechanisms of eRNA-macrophage interaction and related signal transduction pathways. Siglec-1 thereby may provides a new target to treat eRNA-mediated vascular diseases.


Author(s):  
Ramazan Mert Atan ◽  
Uğur Günşen

Inflammation usually occurs as a result of imbalances between pro-inflammatory and anti-inflammatory cytokines. Diet is one of the factors that play a role in their development and prevent them from developing. Therefore, it is important to determine the pro- and anti-inflammatory properties of foods. Diet is an important and modifiable determinant of chronic diseases. There is a lot of scientific evidence to support the fact that foods consumed have positive and negative effects on individuals' health. In addition to being effective whole of diet, it is seen that the food groups contained in the diet affect the inflammatory biomarkers separately. This section provides information about dietary inflammatory index (DII) and diets that are effective on inflammation.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P&lt;0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation


2019 ◽  
Vol 8 (12) ◽  
pp. 2211 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Johannes Gahn ◽  
Barbara Kubin ◽  
Michael Nemec ◽  
...  

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)2D3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)2D3 on the proliferation of allogenic CD4+ T lymphocyte or on the functional status of primary CD68+ macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)2D3 on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)2D3 increased or decreased CD4+ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)2D3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)2D3 significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)2D3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.


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