Acute Immunomodulatory Effects of Fentanyl and its Three New Analogues in Swiss Albino Mice

2017 ◽  
Vol 3 (1) ◽  
pp. 24 ◽  
Author(s):  
Shiv Kumar Yadav ◽  
Rahul Bhattacharya
Keyword(s):  
Pain Management ◽  
Opioid Receptor ◽  
Inflammatory Cytokines ◽  
Opioid Analgesic ◽  
Interleukin 10 ◽  
Acute Effect ◽  
Post Exposure ◽  
Tnf Α ◽  
Pre Treatment ◽  
Factor Α

Fentanyl is a potent synthetic opioid analgesic. However, due to its several limitations, new analogues are being synthesised for better pain management. We have earlier reported the synthesis and bio-efficacy of fentanyl and its eight new analogues (1-8) in mice. Among eight analogues tested, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. Therapeutic efficacy of fentanyl and its analogues are known to be compromised due to many adverse effects, including alterations in the immune system. Therefore, the present study was undertaken to assess the acute effect of fentanyl and its three analogues (2, 5, and 6) on plasma levels of different pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokines such as interleukin-10 (IL-10) at different time points. Mice were intraperitoneally treated with 0.50 LD50 of the compounds and cytokines were measured 1 h, 2 h, 4 h, and 24 h post-exposure. Compared to control, none of the treatments produced any change in TNF-α and IL-1β levels. However, IL-6 levels were significantly elevated between 1 h to 2 h post-exposure in fentanyl and analogue 2 treated groups. Further, IL-10 levels were found to be significantly increased in fentanyl, analogue 2, and 6 treated groups at 1 h and 2 h post-exposure. Pre-treatment of naltrexone (opioid receptor antagonist) blocked the effects of fentanyl, confirming that its effects were opioid receptor- dependent. However, effect of naltrexone on analogue 2 and 6 was not conclusively evidenced, indicating that immunomodulatory changes caused by the analogues could have some additional implications as well. The present study reveals undesirable effects of fentanyl and its new analogues on cytokines homeostasis, thereby limiting their use in pain management.

scholarly journals Characteristics of cytokine status in the pathogenesis of experimental periodontitis and immobilization stress

2021 ◽  
Vol 11 (8) ◽  
pp. 504-509
Author(s):  
P. Olekshij
Keyword(s):  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Immobilization Stress ◽  
Interleukin 10 ◽  
Tnf Α ◽  
Experimental Periodontitis ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

The aim of our study is to elucidate changes in the content of pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 (IL-10) in the blood serum of guinea pigs in the dynamics of experimental periodontitis and immobilization stress.The dynamics of the combined pathology (experimental periodontitis and immobilization stress) is accompanied by a pronounced progression of the proinflammatory group of cytokines - TNF-α and IL-6 against the background of declining functional activity of IL-10 at all stages of their formation (3 rd , 5 th and 15 th days) with an advantage on the 15 th day of the experiment. The data obtained indicate an imbalance of pro- and anti-inflammatory cytokines and impaired cytokinogenesis, which is important for the pathogenesis in this combined pathology.

scholarly journals High Concentration of Inflammatory Cytokines in the Tears of Patients with Concomitant Strabismus

2020 ◽  
Author(s):  
Xiaoping Hong ◽  
Fadian Ding ◽  
Shirong Huang ◽  
Wei Lian ◽  
Weidong Zheng
Keyword(s):  
Inflammatory Cytokines ◽  
Interleukin 10 ◽  
Control Group ◽  
High Concentration ◽  
Interleukin 17A ◽  
Tnf Α ◽  
Concomitant Strabismus ◽  
Factor Α ◽  
Experimental Group ◽  
Necrosis Factor

Abstract BACKGROUND: Our study aimed to determine whether the expression concentration of inflammatory cytokines in ocular surface tears was increased in patients with concomitant strabismus.METHODS: In this study, the concentration of inflammatory cytokines interleukin-6 (IL-6), interleukin-17A (IL-17A), interleukin-10 (IL-10), interleukin-12p70 (IL-12P70), interferon gamma (INF-γ), and tumor necrosis factor- α (TNF-α) were detected in tears in patients with concomitant strabismus and healthy controls matched by age and gender.RESULTS: Our results showed that the concentration of IL-6 and TNF-α were significantly higher in the experimental group compared to the normal group. The concentration of IL-17A, IL-10, IL-12p70, and INF-γ in patients with concomitant strabismus were higher than those in the control group, but not reached the statistically significant.CONCLUSIONS: Our results suggested that most of concomitant strabismus patients have higher concentration of inflammatory cytokines in tears.

scholarly journals Correlation Between Tumor-Associated Macrophage and Inflammatory Factors in Lymphoma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5132-5132
Author(s):  
Xiaolin Sun ◽  
Jun Ni ◽  
Hong Wang ◽  
Xin Sun ◽  
Cuimei Wang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Risk Group ◽  
Interleukin 10 ◽  
High Risk Group ◽  
Macrophage Phenotype ◽  
Tumor Associated Macrophage ◽  
Tumor Tissues ◽  
Tnf Α ◽  
Different Types ◽  
Factor Α

Abstract Introduction To study the expression of tumor associated macrophage (TAMs), inflammatory cytokines IL-1β (interleukin-lβ), TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) and IL-10 (interleukin 10) and its significance in different types of lymphoma in lymph node pathological tissue. Methods 106 cases of clinical pathology specimens of patients were collected from different types and different staging classifications. The expressions of tumor-associated macrophage and interleukin-1β (IL-1β), tumor nec.rosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in lymphoma tissues were detected by immunohistochemical staining; Results Both CD68 and CSF-1R showed high expression in lymphoma tumor tissues. The positive rates of CD68 and CSF-1R in Ⅳ period patients was higher than Ⅱperiod (P <0.05), and the level of CSF-1R in high-risk group was higher than low-risk group (P <0.05). The expression of CD68 was positively correlated with CSF-1R. The inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-10 were highly expressed in tumor tissues; the positive rate of IL-1β in lymphoma IV period was higher than periodⅡ(P <0.05) and the level of IL- 6 in high-risk group were significantly higher than the low-risk group (P <0.05).The expression of tumor-associated macrophage phenotype CD68 in lymphoma tissues was positively correlated with inflammatory cytokines IL-1β, TNF-α, and IL-6 (P <0.05). Conclusion 1.CD68, tumor-associated macrophage phenotype, and CSF-1R were highly expressed in lymphoma tissues 2.The expression of CD68 was positively correlated with inflammatory cytokines. 3.TAMs were involved in tumor inflammatory microenvironment. Funded by Jiangsu Provincial Special Program of Medical Science (BL2012005) Disclosures No relevant conflicts of interest to declare.

scholarly journals Serum biochemical and inflammatory cytokines in a rat model of metabolic syndrome

2020 ◽  
Vol 11 (4) ◽  
pp. 46-52
Author(s):  
Mohammed Haruna Yeldu ◽  
Ahmed Mus’ab
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Interleukin 10 ◽  
Treated Group ◽  
Tnf Α ◽  
Serum Biochemical ◽  
Factor Α

Background: Metabolic syndrome (MetS) is a combination of cardio-metabolic risk factors including obesity, hyperglycaemia, dyslipidaemia, oxidative stress and hypertension.  Aims and Objectives: This study was aimed at determining the serum concentrations of biochemical and inflammatory cytokines and assesses the correlation between the biochemical and inflammatory cytokines in a rat model of metabolic syndrome. Materials and Methods: Twenty rats were divided into 2 groups of 10 each: control (fructose untreated) and the fructose treated group. MetS was induced by oral administration of 10% fructose in water for 32 weeks. At the end of the experiment, rats were fasted for 12 hours and blood samples collected and body weight, body mass index (BMI), fasting blood glucose (FBG), serum lipid profile, interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α) were measured using standard techniques. Result: Result indicated significantly (P< 0.05) increased FBG, body weight, BMI, serum TC and LDL-C while, HDL-C levels significantly (P< 0.05) decreased in MetS group compared with controls. However, the levels of VLDL-C, TG and AIX were not significantly (P > 0.05) different between the groups. Significantly (P< 0.05) increased serum IL-6, IL-10 and TNF-α were observed in MetS group compared with controls. Serum IL-10 and TNF- α were inversely correlated with BMI. Serum IL-10 negatively correlated with FBG while, IL-6 was not correlated with either of BMI and FBG.Serum AIX and VLDL-C were positively correlated with TG while, HDL-C level was inversely correlated with TG. With the exception of serum LDL-C which positively correlated with TC, significant  correlation was not established between serum TC and each of AIX, HDL-C and VLDL-C. Conclusion: The rat model of MetS was established after treatment with 10% fructose in water. This plays an important role in the pathogenesis of components of metabolic syndrome, including dyslipidaemia, hyperglycaemia and obesity; and serum IL-6, IL-10 and TNF- α are raised in metabolic syndrome and this underscores the role of these cytokines in inflammation associated with metabolic syndrome.

scholarly journals Chlorogenic Acid and Geniposide Combination Prevents NASH in Rats Fed High-fat diet via Microbiota and TLR4-LPS Pathway

2021 ◽  
Author(s):  
Zhijia Zhou ◽  
Lingxia Xu ◽  
Shaoliang Zhang ◽  
Shilin Xu ◽  
Yanmiao Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Chlorogenic Acid ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Oral Treatment ◽  
Variable Region ◽  
High Fat ◽  
Tnf Α ◽  
Abundance And Diversity ◽  
Factor Α

Abstract Objective: Chlorogenic acid and geniposide (CG) are derived from traditional Chinese medicine, Yinchenhao Recipe (QCHR), and can improve the clinical efficacy of NASH patients. This study investigated the effects of CG on NASH and expounded its Potential mechanism of action through the LPS-TLR4 pathway and microbiota. Methods: Rats were randomized into Control (C), Model (M), Chlorogenic Acid and Geniposide (CG), Pioglitazone (PH) and Bifico (B) groups. After an 8-week high-fat diet (HFD), CG, PH and B oral treatment were initiated and carried out for a further 8 weeks. The stool samples were used in a16S rDNA V4 highly variable region measurement method in order to regulate the role of CG in gut microbiota. The concentrations of triglyceride (TG), cholesterol (CHO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in LPS were detected by the corresponding methods. Results: Observations were made that CG significantly improved the pathology of the liver and terminal ileum tissue. The accumulation of TG and the content of inflammatory cytokines in the liver were significantly decreased and the abundance of Proteobacteria was significantly down-regulated. The expression of TLR4, AP-1, MyD88, and phosphorylated NF-κB p65 were significantly decreased. All the findings above indicated that CG was highly effective in improving the composition of gut microbiota, decreasing the production of endogenous LPS, and reducing the secretion of inflammatory cytokines through the gut-liver axis.Conclusion: CG can regulate the abundance and diversity of the intestinal microbial community and improve liver inflammation and steatosis in NASH rats by reducing LPS-TLR4-mediated inflammation.

Abstract 620: Angiotensin AT2 Receptor Exerts an Anti-inflammatory Response in Lipopolysaccharide-activated THP-1 Macrophages

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Isha S Dhande ◽  
Tahir Hussain
Keyword(s):  
Inflammatory Response ◽  
Interleukin 10 ◽  
Receptor Expression ◽  
Human Macrophage ◽  
No Production ◽  
At2 Receptor ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pre Treatment ◽  
Lps Activation

Macrophages have been shown to be an important contributor to the pathogenesis of hypertension and stroke. The angiotensin AT2 receptor (AT2R), which is expressed in macrophages, is known to promote vasodialation, natriuresis and lower inflammation. The goal of the present study was to explore the anti-inflammatory role of AT2R stimulation in human macrophage-like THP-1 cells activated by lipopolysaccharide (LPS). Phorbol 12-myristate 13-acetate (PMA) differentiated macrophage-like THP-1 cells were treated with AT2R agonist C21 (1 μmol/L) for 30 minutes prior to activation with LPS (1 μg/ml). Media and cells were collected after 24 hours and were analyzed for levels of pro- and anti-inflammatory cytokines and proteins. Pre-treatment with C21 resulted in a 4-fold increase (104.8±6.1 vs 406.7±52.3) in anti-inflammatory interleukin-10 (IL-10) production and a 5-fold decrease (3560±237 vs 588.8±15.94) in pro-inflammatory tumor necrosis factor-α (TNF-α) levels in the media in response to LPS. Predictably, LPS resulted in a 6-fold up-regulation of iNOS expression which was prevented with C21 pre-treatment. A modest decrease in the anti-inflammatory macrophage mannose receptor C type 2 (MRC2) expression was detected with LPS treatment. AT2R agonist pre-treatment, however, increased this receptor expression by ~70% after LPS activation. C21 alone also resulted in a 20% increase in MRC2 expression compared to untreated controls. The anti-inflammatory effect of AT2R activation was abolished in the presence of neutralizing IL-10 antibody (1 μg/ml), indicating a central role for IL-10 in mediating the beneficial response to C21 in LPS activated macrophages. Further, inhibition of nitric oxide (NO) by L-NAME prior to C21 pre-treatment also prevented the decrease in TNF-α and increase in IL-10 in response to AT2R agonist, which suggests that the anti-inflammatory response to C21 may be mediated via increase in NO production prior to LPS activation of macrophages. In conclusion, AT2R stimulation may potentially suppress the inflammatory response of macrophages to LPS by shifting the balance from pro- to anti-inflammatory cytokine production and may prove to be beneficial in the control of the inflammatory component of stroke and hypertension.

Predisposition to Hyperthyroidism May Be Influenced by Functional TNF-α, IL-1, IL-6, and IL-10 Polymorphisms: A Meta-Analysis

2020 ◽  
Vol 181 (12) ◽  
pp. 956-965
Author(s):  
Hong Ma ◽  
Ting Tan ◽  
Jie Wu ◽  
Juan Chen ◽  
Xiaohong Zhang
Keyword(s):  
Meta Analysis ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Asian Origin ◽  
Tnf Α ◽  
Caucasian Origin ◽  
Meta Analyses ◽  
Factor Α ◽  
Necrosis Factor

<b><i>Background:</i></b> Predisposition to hyperthyroidism may be influenced by functional gene polymorphisms in tumor necrosis factor-α (<i>TNF-α</i>), interleukin-1 (<i>IL-1</i>), interleukin-4 (<i>IL-4</i>), interleukin-6 (<i>IL-6</i>), and interleukin-10 (<i>IL-10</i>). However, the results of the studies published so far remain discrepant, so we conducted a meta-analysis to more robustly investigate relationships between <i>TNF-α</i>/<i>IL-1/IL-4/IL-6/IL-10</i> polymorphisms and predisposition to hyperthyroidism. <b><i>Methods:</i></b> A comprehensive literature retrieval from PubMed, Embase, Web of Science, WanFang, VIP, and CNKI was endorsed by the authors, and 38 studies were found to be eligible for pooled meta-analyses. <b><i>Results:</i></b> We found that genotypic frequencies of <i>TNF-α</i> −308 G/A, <i>IL-1A</i> −889 C/T, <i>IL-6</i> −174 G/C, <i>IL-6</i> −572 G/C, <i>IL-10</i> −819 C/T, and <i>IL-10</i> −1082 A/G polymorphisms among cases were significantly different from those among controls. Moreover, we also found that genotypic frequencies of <i>TNF-α</i> −308 G/A and <i>IL-6</i> −174 G/C polymorphisms among cases of Caucasian origin were significantly different from those among Caucasian controls, and genotypic frequencies of <i>IL-1A</i> −889 C/T, <i>IL-1B</i> −511 C/T, <i>IL-6</i> −174 G/C, <i>IL-6</i> −572 G/C, and <i>IL-10</i> −1,082 A/G polymorphisms among cases of Asian origin were also significantly different from those among Asian controls. <b><i>Conclusions:</i></b> This meta-analysis suggests that <i>TNF-α</i> −308 G/A, <i>IL-1A</i> −889 C/T, <i>IL-1B</i> −511 C/T, <i>IL-6</i> −174 G/C, <i>IL-6</i> −572 G/C, <i>IL-10</i> −819 C/T, and <i>IL-10</i> −1,082 A/G polymorphisms may influence predisposition to hyperthyroidism in certain ethnic groups.

scholarly journals Acute Effect of a Single Dose of Tomato Sofrito on Plasmatic Inflammatory Biomarkers in Healthy Men

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 851 ◽  
Author(s):  
Sara Hurtado-Barroso ◽  
Miriam Martínez-Huélamo ◽  
Jose Fernando Rinaldi de Alvarenga ◽  
Paola Quifer-Rada ◽  
Anna Vallverdú-Queralt ◽  
...  
Keyword(s):  
Single Dose ◽  
Bioactive Compounds ◽  
Acute Effect ◽  
Inflammatory Biomarkers ◽  
Positive Health ◽  
Reactive Protein ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Factor Α ◽  
Antioxidant Diet

Sofrito is a Mediterranean tomato-based sauce that typically also contains olive oil, onion, and garlic. The preparation of sofrito modifies the bioactive compounds (carotenoids and polyphenols) in the ingredients to more bioavailable forms, promoting cis-lycopene formation and polyphenol bioaccessibility. To evaluate the health benefits of this cooking technique, the effect of consuming an acute dose of sofrito on the inflammatory status was studied. In a clinical trial, 22 healthy male subjects consumed a single dose of sofrito (240 g/70 kg) after three days without ingesting any tomato products and following a low-antioxidant diet the day before the intervention. Plasma carotenoids and total polyphenol excretion (TPE) were evaluated, as well as the inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α). After the sofrito intake, a significant decrease in CRP (p = 0.010) and TNF-α (p = 0.011) was observed, but only TNF-α was inversely correlated with an increase in TPE and plasma β-carotene (not the major carotenoid, lycopene). The positive health effects of this tomato-based product may be attributed not only to lycopene, but to the bioactive compounds of all the ingredients.

Activation of oxytocin receptor in the trigeminal ganglion attenuates orofacial ectopic pain attributed to inferior alveolar nerve injury

2020 ◽  
Author(s):  
Chao-Lan Huang ◽  
Fei Liu ◽  
Yan-Yan Zhang ◽  
Jiu Lin ◽  
Min Fu ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Trigeminal Ganglion ◽  
Inferior Alveolar Nerve ◽  
Oxytocin Receptor ◽  
Mechanical Hypersensitivity ◽  
Tnf Α ◽  
Whisker Pad ◽  
Pre Treatment ◽  
Spinal Trigeminal Nucleus Caudalis ◽  
Factor Α

Oxytocin receptor (OXTR), a G protein-coupled receptor, has been demonstrated to play a significant role in analgesia after activation by its canonical agonist, oxytocin (OXT) in the dorsal root ganglion (DRG). However, the role of OXTR in the trigeminal nervous system on the orofacial neuropathic pain is still little known. In the present study, we aimed to investigate the regulation effect and mechanism of OXTR in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) on orofacial ectopic pain induced by trigeminal nerve injury. Inferior alveolar nerve (IAN) was transected to establish trigeminal ectopic pain model. Von Frey filaments behavioral test demonstrated IAN transection (IANX) evoked mechanical hypersensitivity in the whisker pad since from day 1 to at least day 14 after surgery. In addition, administration of OXT (50 μM and 100 μM) into the TG attenuated the mechanical hypersensitivity induced by IANX, which was reversed by pre-treatment with L-368,899 (a selective antagonist of OXTR) into the TG. In addition, immunofluorescence (IF) showed the expression of OXTR in neurons in the TG and SpVc. Furthermore, western blot (WB) analysis indicated that the upregulated expression of OXTR, calcitonin gene-related peptide (CGRP), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the TG and SpVc after IANX was inhibited by the administration of OXT into the TG. And the inhibition effect of OXT on the expression of CGRP, IL-1β, and TNF-α was abolished by pre-application of L-368,899 into the TG.

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