scholarly journals Human Models of Low-Grade Inflammation: Bolus versus Continuous Infusion of Endotoxin

2007 ◽  
Vol 14 (3) ◽  
pp. 250-255 ◽  
Author(s):  
S. Taudorf ◽  
K. S. Krabbe ◽  
R. M. G. Berg ◽  
B. K. Pedersen ◽  
K. Møller
Keyword(s):  
Continuous Infusion ◽  
Inflammatory Mediators ◽  
Low Dose ◽  
Bolus Injection ◽  
In Vivo Model ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Endotoxin Infusion ◽  
Tnf Α ◽  
Low Grade Inflammation

ABSTRACT Systemic low-grade inflammation is recognized in an increasing number of chronic diseases. With the aim of establishing an experimental human in vivo model of systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (0.3 ng/kg of body weight) either as a bolus injection or as a 4-h continuous intravenous infusion, as well as after saline administration, in 10 healthy male subjects on three separate study days. Only bolus endotoxin caused an increase in heart rate, whereas a slight increase in rectal temperature was observed in both endotoxin groups. Tumor necrosis factor alpha (TNF-α), interleukin-6, and neutrophil responses were earlier and more pronounced in the bolus trial compared with the infusion trial results, whereas lymphocytes increased after endotoxin bolus injection as well as infusion without any difference between groups. Finally, endotoxin activated the hypothalamo-pituitary-adrenal axis slightly earlier in the bolus compared to the infusion trial. The continuous endotoxin infusion model may be more representative of human low-grade inflammation than the bolus injection model due to a less dynamic and more sustained increase in circulating levels of inflammatory mediators over time. In conclusion, low-dose endotoxin infusion elicits an inflammatory response, as assessed by a rise in TNF-α, and the responses are significantly different according to whether low-dose endotoxin is applied as a bolus injection or as a continuous infusion.

scholarly journals Cardiorenal Syndrome in Hypertensive Rats: Microalbuminuria, Inflammation and Ventricular Hypertrophy

2012 ◽  
pp. 13-24 ◽  
Author(s):  
M. MOUBARAK ◽  
H. JABBOUR ◽  
V. SMAYRA ◽  
E. CHOUERY ◽  
Y. SALIBA ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Cardiorenal Syndrome ◽  
Left Ventricular ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Reactive Protein ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Factor Alpha ◽  
Low Grade Inflammation

The aim of our study was to evaluate a possible association between microalbuminuria (MA), several low-grade inflammation factors and left ventricular hypertrophy (LVH) by using a pharmacological approach. This may provide new insights into the pathophysiologic mechanisms of the cardiorenal syndrome (CRS) linking early renal impairment with elevated cardiovascular risk. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (220-250 g). After the development of hypertension, rats were divided into four groups: 2K-1C (untreated), calcium channel blocker (amlodipine-treated), angiotensin receptor blocker (losartan-treated) and peripheral vasodilator (hydralazine-treated), which were treated for 10 weeks. Rats in the 2K-1C group had all developed hypertension, a significant increase in plasma levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), brain natriuretic peptide (BNP) and C-reactive protein (CRP). Moreover MA and creatininaemia underwent a significant increase. Under treatment decreases were observed in systolic blood pressure (SBP), TNF-α, CRP, IL-6, BNP concentrations and creatininaemia. These results were related to the absence of MA which was significantly associated with reductions in cardiac mass and hypertrophy markers (BNP and β-MHC gene expression) as well as renal interstitial inflammation. In conclusion, our results suggest that the reduction of MA is correlated with the decrease of the inflammatory components and seems to play an important role in protecting against cardiac hypertrophy and renal injury.

scholarly journals Lipopolysaccharide influence on leptin hormone and tumor necrosis factor-alpha release from human adipose tissue

2018 ◽  
Vol 16 ◽  
pp. 205873921877497
Author(s):  
Sa’ad Al-Lahham ◽  
Nidal Jaradat ◽  
Malik Al-Qub ◽  
Abdallah Hamayel ◽  
Abdalrahman Assaassa ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Low Grade Inflammation ◽  
Necrosis Factor

Obesity is associated with low-grade inflammation that originates mainly from adipose tissue. This is implicated in the pathogenesis of type-2 diabetes and cardiovascular diseases. Strong evidence indicates that chronically elevated systemic low-grade lipopolysaccharide (LPS), elicits low-grade inflammation. However, evidence on LPS effect on adipokines’ level, such as leptin, is scarce, and it has never been investigated ex vivo in human subcutaneous adipose tissue (SAT) and therefore we aim to investigate this. To achieve our aim, SAT explants were obtained from 12 patients (50% males) and were treated with/without LPS. Protein concentration was determined by enzyme-linked immunosorbent assay (ELISA). We found that the average age and body mass index (BMI) of included patients were 58.6 years and 28.6 kg/m2, respectively. LPS induced significantly (~3×, P < 0.0001) the secretion of tumor necrosis factor (TNF)-α from SAT, and it was not associated with age or BMI. However, leptin secretion was inhibited slightly (~20%), but significantly. Interestingly, leptin release was significantly inhibited (~50%) in SAT from lean but not from obese patients, and there was an association between leptin response and BMI (R = 0.8), but no association with age. In this study, we found, for the first time, that LPS suppresses the release of leptin hormone from SAT obtained from lean patients, while it induces TNF-α release. Our findings provide extra evidence and confirm earlier studies regarding the role of LPS in low-grade inflammation. Further investigations are essential to identify factors that inhibit LPS passage through intestinal barrier in order to prevent or reduce the development of obesity and its associated chronic diseases.

scholarly journals Polyphenols from Passiflora ligularis Regulate Inflammatory Markers and Weight Gain

2021 ◽  
Vol 12 (1) ◽  
pp. 36-45
Author(s):  
Jaime Angel-Isaza ◽  
Juan Carlos Carmona-Hernandez ◽  
William Narváez-Solarte ◽  
Clara Helena Gonzalez-Correa
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Wistar Rats ◽  
Adult Population ◽  
Control Group ◽  
Chow Diet ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Low Grade Inflammation

Abstract Weight-related disorders affect more than half of the adult population worldwide; they are also concomitant with a state of chronic low-grade inflammation manifesting in abnormal cytokine production. The present study evaluated the effect of polyphenol and flavonoid extract from Passiflora ligularis (granadilla) on low-grade inflammation and body weight in overweight Wistar rats. To induce weight-gain, rats were fed a chow diet with 30% sucrose water and supplemented with 2.0, 2.5, and 3.0 g/L polyphenol extracts (n = 16). The design was a 3 +1 factorial model performed for 42 days (granadilla polyphenols, 3 levels of supplementation, and 1 control group). In addition to total polyphenol and total flavonoid content, the major identified and quantified polyphenol, via UHPLC, was ferulic acid. Interleukin 6 (IL-6), and cytokine tumor necrosis factor-alpha (TNF-α) were evaluated in serum. A decline in the concentration of TNF-α and in weight-gain was found in P. ligularis (granadilla) groups treated with the 2.5 g/L dose. Consumption of polyphenol extracts from granadilla inhibits interleukin-activity as an indicator of inflammation and aids in body-weight control, considering similar food intake, in overweight Wistar rats.

scholarly journals Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Low Dose ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

IL-6 as a Surrogate Biomarker: The IL-6 Clinical Value for the Diagnosis of Insulin Resistance and Type 2 Diabetes.

2021 ◽  
pp. 1-13
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Low Grade ◽  
Clinical Value ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Low Grade Inflammation

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus (T2D). It occurs as a result of lipid disorders and increased levels of circulating free fatty acids (FFAs). FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased levels fatty acid has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes. Among the biomarkers that are accompanying low grade inflammation include IL-1β, IL-6 and TNF-α. The current review point out the importance of measuring the inflammatory biomarkers especially focusing on the conductance and measurement for IL-6 as a screening laboratory test and its diagnostic value in clinical practice.

scholarly journals Role of Hck in the Pathogenesis of Encephalomyocarditis Virus-Induced Diabetes in Mice

2001 ◽  
Vol 75 (4) ◽  
pp. 1949-1957 ◽  
Author(s):  
K. S. Choi ◽  
H. S. Jun ◽  
H. N. Kim ◽  
H. J. Park ◽  
Y. W. Eom ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Kinase Inhibitor ◽  
Src Kinase ◽  
Encephalomyocarditis Virus ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Necrosis Factor Alpha ◽  
Diabetes In Mice ◽  
Tnf Α

ABSTRACT Soluble mediators such as interleukin-1β, tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) produced from activated macrophages play an important role in the destruction of pancreatic β cells in mice infected with a low dose of the D variant of encephalomyocarditis (EMC-D) virus. The tyrosine kinase signaling pathway was shown to be involved in EMC-D virus-induced activation of macrophages. This investigation was initiated to determine whether the Src family of kinases plays a role in the activation of macrophages, subsequently resulting in the destruction of β cells, in mice infected with a low dose of EMC-D virus. We examined the activation of p59/p56Hck, p55Fgr, and p56/p53Lynin macrophages from DBA/2 mice infected with the virus. We found that p59/p56Hck showed a marked increase in both autophosphorylation and kinase activity at 48 h after infection, whereas p55Fgr and p56/p53Lyn did not. The p59/p56Hck activity was closely correlated with the tyrosine phosphorylation level of Vav. Treatment of EMC-D virus-infected mice with the Src kinase inhibitor, PP2, resulted in the inhibition of p59/p56Hck activity and almost complete inhibition of the production of TNF-α and iNOS in macrophages and the subsequent prevention of diabetes in mice. On the basis of these observations, we conclude that the Src kinase, p59/p56Hck, plays an important role in the activation of macrophages and the subsequent production of TNF-α and nitric oxide, leading to the destruction of pancreatic β cells, which results in the development of diabetes in mice infected with a low dose of EMC-D virus.

scholarly journals The Cooperative Induction of CCL4 in Human Monocytic Cells by TNF-α and Palmitate Requires MyD88 and Involves MAPK/NF-κB Signaling Pathways

2019 ◽  
Vol 20 (18) ◽  
pp. 4658 ◽  
Author(s):  
Sindhu ◽  
Kochumon ◽  
Shenouda ◽  
Wilson ◽  
Al-Mulla ◽  
...  
Keyword(s):  
Low Grade ◽  
Monocytic Cells ◽  
Signaling Mechanism ◽  
Blocking Antibody ◽  
Metabolic Inflammation ◽  
Qrt Pcr ◽  
Signaling Mechanisms ◽  
Tnf Α ◽  
Low Grade Inflammation ◽  
Tlr4 Receptor

: Chronic low-grade inflammation, also known as metabolic inflammation, is a hallmark of obesity and parallels with the presence of elevated circulatory levels of free fatty acids and inflammatory cytokines/chemokines. CCL4/MIP-1β chemokine plays a key role in the adipose tissue monocyte recruitment. Increased circulatory levels of TNF-α, palmitate and CCL4 are co-expressed in obesity. We asked if the TNF-α/palmitate could interact cooperatively to augment the CCL4 production in human monocytic cells and macrophages. THP-1 cells/primary macrophages were co-treated with TNF-α/palmitate and CCL4 mRNA/protein expression was assessed using qRT-PCR/ELISA. TLR4 siRNA, a TLR4 receptor-blocking antibody, XBlue™-defMyD cells and pathway inhibitors were used to decipher the signaling mechanisms. We found that TNF-α/palmitate co-stimulation augmented the CCL4 expression in monocytic cells and macrophages compared to controls (p < 0.05). TLR4 suppression or neutralization abrogated the CCL4 expression in monocytic cells. Notably, CCL4 cooperative induction in monocytic cells was: (1) Markedly less in MyD88-deficient cells, (2) IRF3 independent, (3) clathrin dependent and (4) associated with the signaling mechanism involving ERK1/2, c-Jun, JNK and NF-κB. In conclusion, TNF-α/palmitate co-stimulation promotes the CCL4 expression in human monocytic cells through the mechanism involving a TLR4-MyD88 axis and MAPK/NF-κB pathways. These findings unravel a novel mechanism of the cooperative induction of CCL4 by TNF-α and palmitate which could be relevant to metabolic inflammation.

scholarly journals Lipopolysaccharide-Induced Biliary Factors Enhance Invasion of Salmonella enteritidis in a Rat Model

2000 ◽  
Vol 68 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Abul F. M. W. Islam ◽  
Nathan D. Moss ◽  
Yung Dai ◽  
Murray S. R. Smith ◽  
Andrew M. Collins ◽  
...  
Keyword(s):  
Rat Model ◽  
Inflammatory Mediators ◽  
Salmonella Enteritidis ◽  
Bacterial Invasion ◽  
Mesenteric Lymph Nodes ◽  
Necrosis Factor Alpha ◽  
Lps Challenge ◽  
Hepatobiliary System ◽  
Duct Ligation ◽  
Tnf Α

ABSTRACT In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 106to 107 CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 μg/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P< 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-α) concentrations were measured by bioassay. Biliary concentrations of TNF-α rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-α cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

Differential Effects of Corticosteroids on The Expression of Cyclooxygenase-2, Tumour Necrosis Factor-Alpha and Matrix Metalloproteinase-9 in An Animal Model of Migraine

Cephalalgia ◽  
2008 ◽  
Vol 28 (11) ◽  
pp. 1179-1187 ◽  
Author(s):  
G-M Kim ◽  
K-S Jin ◽  
C-S Chung
Keyword(s):  
Animal Model ◽  
Inflammatory Mediators ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Cox 2 ◽  
Metalloproteinase 9 ◽  
Necrosis Factor

Nitric oxide (NO) directly activates trigeminal afferents innervating the dura mater and up-regulates inflammatory mediators. We evaluated NO-mediated up-regulation of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9), and the effect of glucocorticoid administration in an experimental animal model of migraine. COX-2 and TNF-α expression and MMP-9 activity were increased after continuous intravenous infusion of glyceryl trinitrate (GTN), a NO donor. Immunofluorescence staining demonstrated strong expression of these inflammatory mediators in the meningeal blood vessels. Methylprednisolone (MP) down-regulated MMP-9, which was reversed by RU486, a glucocorticoid receptor antagonist. COX-2 and TNF-α expression was not affected by MP or RU486 administration. These results suggest proinflammatory mediators are involved in the NO-mediated cascade of migraine pathogenesis. Further understanding of the activation of these inflammatory mediators at the transcriptional level may have therapeutic implications for future migraine treatments.

Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes

2012 ◽  
Vol 109 (1) ◽  
pp. 43-49 ◽  
Author(s):  
K. Olli ◽  
S. Lahtinen ◽  
N. Rautonen ◽  
K. Tiihonen
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Markers ◽  
Mrna Level ◽  
Low Grade ◽  
Human Adipocytes ◽  
Low Oxygen ◽  
Hypoxic Conditions ◽  
Tnf Α ◽  
Oxygen Conditions ◽  
Low Grade Inflammation

Obesity is characterised by a state of chronic low-grade inflammation and the elevated circulating and tissue levels of inflammatory markers, including inflammation-related adipokines, released from white adipose tissue. The expression and release of these adipokines generally rises as the adipose tissue expands and hypoxic conditions start to develop within the tissue. Here, the effect of betaine, a trimethylglycine having a biological role as an osmolyte and a methyl donor, on the expression of inflammation-related markers was tested in human adipocytes under hypoxia. Differentiated adipocytes were cultivated under low (1 %) oxygen tension for 8–20 h. The expression of different adipokines, including IL-6, leptin, PPARγ, TNF-α and adiponectin, was measured by quantitative PCR by determining the relative mRNA level from the adipocytes. Hypoxia, in general, led to a decrease in the expression of PPARγ mRNA in human adipocytes, whereas the expression levels of leptin and IL-6 mRNA were substantially increased by hypoxia. The cultivation of adipocytes under hypoxia also led to a reduction in the expression of TNF-α mRNA. The results showed that hypoxia increased the relative quantification of leptin gene transcription, and that betaine (250 μmol/l) reduced this effect, caused by low oxygen conditions. Under hypoxia, betaine also reduced the mRNA level of the pro-inflammatory markers IL-6 and TNF-α. These results demonstrate that the extensive changes in the expression of inflammation-related adipokines in human adipocytes caused by hypoxia can be diminished by the presence of physiologically relevant concentrations of betaine.

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