MDMA (“Ecstasy”) suppresses the innate IFN-γ response in vivo: A critical role for the anti-inflammatory cytokine IL-10

2007 ◽  
Vol 572 (2-3) ◽  
pp. 228-238 ◽  
Author(s):  
Noreen T. Boyle ◽  
Thomas J. Connor
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Zhao ◽  
T Zhang ◽  
X Guo ◽  
C C Wang ◽  
T C Li

Abstract Study question To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. Summary answer:Successful implantation is associated with transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy.What is known already: Immunomodulation is thought to be important for the prevention of rejection of the implanting semi-allograft embryo and successful establishment of pregnancy. A successful pregnancy is characterized by a dominance of anti-inflammatory cytokine profile in the peripheral blood in the first and second trimesters of pregnancy. It is achieved by a complex interplay between various immune cells and cytokines at the fetal-maternal interface, among which the key-players are interleukine–10 (IL–10) and transforming growth factor-β1 (TGF-β1). The circulating inflammatory response in the first few days after embryo transfer to the pathophysiology of implantation failure remains unclear. Study design, size, duration: This prospective observational and longitudinal study on 47 women with infertility was performed in an in vitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. Participants/materials, setting, methods Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)–2, IL–4, IL–10, IL–12, IL–13, IL–17, IL–18, and IL–22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-β1) was measured using commercial enzyme-linked immunosorbent assay kits. Main results and the role of chance The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL–17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL–10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-β1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL–17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL–17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL–10 and TGF-β1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed. Limitations, reasons for caution This is an observational study on peripheral blood cytokine levels, so it is not possible to draw conclusions if the implantation failure is due primarily to failure of the embryo to elicit a trigger for the switch or failure of maternal response to a normal trigger released by the embryo. Wider implications of the findings: The characteristic change in peripheral cytokine profile during successful implantation, well before confirmation of pregnancy, may provide an opportunity to develop serum biomarkers to monitor implantation and to understand the mechanism of its failure, especially in women who experience recurrent implantation failure after IVF. Trial registration number Not applicable


2020 ◽  
Vol 4 ◽  
pp. 239784732097204 ◽  
Author(s):  
Solomon E Owumi ◽  
Abigail O Ijadele ◽  
Uche O Arunsi ◽  
Oyeronke A Odunola

The anti-neoplastic use of Doxorubicin (DOX) is hampered by several limitations, including reproductive toxicity. Luteolin (LUT)–a phytochemical-biological benefits include antioxidative and anti-inflammatory actions. Here we examined the protective effect of LUT against DOX-induced reproductive toxicity in an in vivo model—male albino Wistar rats—randomly assigned to five groups and treated as follows: Control (corn oil 2 mL/kg; per os), LUT (100 mg/kg; per os), DOX (2 mg/kg) by intraperitoneal injections, co-treated groups received LUT (50 and 100 mg/kg) with DOX. Treatment with DOX alone, significantly (p > 0.05), reduced biomarkers of testicular function, reproductive hormone levels, testicular and epididymal antioxidant, and anti-inflammatory cytokine. DOX increased (p > 0.05) sperm morphological abnormalities, as well as reactive oxygen and nitrogen species, lipid peroxidation, xanthine oxidase, a pro-inflammatory cytokine, and apoptotic biomarkers. Furthermore, testicular and epididymal histological lesion complemented the observed biochemical changes in treated rats. LUT co-treatment resulted in a dosage-dependent improvement in rats’ survivability, antioxidants capacity, reduction in biomarkers of oxidative stress, pro-inflammatory cytokines, and apoptosis in rat’s testis and epididymis. Also, LUT treatment resulted in improved histological features in the testis and epididymis, relative to DOX alone treated rats. LUT co-treatment abated DOX-mediated reproductive organ injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. LUT supplementation may serve as a phyto-protective agent in alleviating male reproductive organ toxic injuries associated with Doxorubicin therapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Dongzhi Chen ◽  
Wenbin Xu ◽  
Jingfang Teng ◽  
Huifang Liu ◽  
Yuanyuan Wang ◽  
...  

Herein, the migration distribution and safety of specific phenotypic and functionally identified spleen-derived invariant natural killer T2 (iNKT2) cells after adoptive infusion in mice were studied. The proliferation and differentiation of iNKT cells were induced by intraperitoneal injection of α-galactosylceramide (α-GalCer) in vivo. Mouse spleens were isolated in a sterile environment. iNKT cells were isolated by magnetic-activated cell sorting columns (MS columns). Cytometric bead array (CBA) assay was used to detect cytokine secretion in the supernatant stimulated by iNKT cells. The basic life status of the mice was observed, and systematic quantitative scoring was conducted after injecting spleen-derived iNKT cells through the tail vein. An in vivo imaging system was used to trace the migration and distribution of iNKT cells in DBA mice. The percentage of the iNKT2 subgroup was the highest in 3 days after intraperitoneal injection of α-GalCer, and iNKT2 subsets accounted for more than 92% after separation and purification by magnetic-activated cell sorting (MACS). Anti-inflammatory cytokine IL-4 was mainly found in the supernatant of cell cultures. The adoptive infusion of iNKT cells into healthy mice resulted in no significant change in the basic life status of mice compared with the noninjected group. iNKT cells were detected in the lung, spleen, and liver, but no fluorescence was detected in lymph nodes and thymus. After dissecting the mice, it was found that there were no significant abnormalities in the relevant immune organs, brain, heart, kidney, lung, and other organs. Intraperitoneal injection of α-GalCer results in a large number of iNKT2 cells, mainly secreting anti-inflammatory cytokine IL-4, from the spleen of mice. After adoptive infusion, the iNKT2 cells mainly settled in the liver and spleen of mice with a satisfactory safety profile.


2012 ◽  
Vol 108 (10) ◽  
pp. 1746-1755 ◽  
Author(s):  
Yu-Yun Gao ◽  
Qing-Mei Xie ◽  
Ling Jin ◽  
Bao-Li Sun ◽  
Jun Ji ◽  
...  

The present study investigated the effects of xanthophylls (containing 40 % of lutein and 60 % of zeaxanthin) on proinflammatory cytokine (IL-1β, IL-6, interferon (IFN)-γ and lipopolysaccharide-induced TNF-α factor (LITAF)) and anti-inflammatory cytokine (IL-4 and IL-10) expression of breeding hens and chicks. In Expt 1, a total of 432 hens were fed diets supplemented with 0 (as the control group), 20 or 40 mg/kg xanthophylls (six replicates per treatment). The liver, duodenum, jejunum and ileum were sampled at 35 d of the trial. The results showed that both levels of xanthophyll addition decreased IL-1β mRNA in the liver and jejunum, IL-6 mRNA in the liver, IFN-γ mRNA in the jejunum and LITAF mRNA in the liver compared to the control group. Expt 2 was a 2 × 2 factorial design. Male chicks hatched from 0 or 40 mg/kg xanthophyll diet of hens were fed a diet containing either 0 or 40 mg/kg xanthophylls. The liver, duodenum, jejunum and ileum were collected at 0, 7, 14 and 21 d after hatching. The results showed thatin ovoxanthophylls decreased proinflammatory cytokine expression (IL-1β, IL-6, IFN-γ and LITAF) in the liver, duodenum, jejunum and ileum and increased anti-inflammatory cytokine expression (IL-4 and IL-10) in the liver, jejunum and ileum mainly at 0–7 d after hatching.In ovoeffects gradually vanished and dietary effects began to work during 1–2 weeks after hatching. Dietary xanthophylls modulated proinflammatory cytokines (IL-1β, IL-6 and IFN-γ) in the liver, duodenum, jejunum and ileum and anti-inflammatory cytokine (IL-10) in the liver and jejunum mainly from 2 weeks onwards. In conclusion, xanthophylls could regulate proinflammatory and anti-inflammatory cytokine expression in different tissues of hens and chicks.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Venkateswara R Gogulamudi ◽  
Umadevi Subramanian ◽  
Meaghan Bloodworth ◽  
Kailash N Pandey

Disruption of natriuretic peptide receptor-A (NPRA) gene ( Npr1 ) activates the pro-inflammatory responses, which contributes to the pathogenesis of hypertension and end-organ damage. The objective of this study was to determine the kinetic responses of pro- and anti-inflammatory cytokines in Npr1 gene-knockout (KO) mice. Npr1 0-copy ( Npr1 -/- ), 1-copy ( Npr1 +/- ), and 2-copy ( Npr1 +/+ ) mice were pre-treated with rapamycin and multiplex analyses were done to assess cytokines levels. Pro-inflammatory cytokine, IFN-γ protein levels in plasma and kidney of 0-copy and 1-copy mice were markedly higher compared with 2-copy mice (76±1; 49±2 vs 32±1.3 pg/ml; 79±2; 29±1 vs. 27±0.5 pg/mg, respectively). Similarly, IL-6 levels in plasma and kidney were significantly elevated in 0-copy and 1-copy mice than 2-copy mice (52±1; 27±0.5 vs.12±0.4 pg/ml; 49±1.5; 38±2 vs.18±1.1 pg/mg, respectively). Interestingly, anti-inflammatory cytokine IL-5 protein levels in plasma and kidneys were significantly down-regulated in 0-copy and 1-copy mice than 2-copy mice (6±0.8; 5±0.1 vs. 12±0.5 pg/ml; 6±0.6; 9±0.4 vs. 28±0.5 pg/mg). IL-10 levels in plasma and kidney of 0-copy and 1-copy mice were also significantly decreased than 2-copy mice (22±0.4; 39±1 vs. 62±3 pg/ml; 14±1.7; 36±0.2 vs. 52±3 pg/mg). Rapamycin significantly reduced the levels of IFN- γ in plasma and kidney of 0-copy (50%, 35%) and 1-copy (63%, 55%) mice and IL-6 level in 0-copy (60%, 38%) and in 1-copy (40%, 26%) mice compared with 2-copy mice. In contrast, rapamycin treatment significantly elevated IL-5 levels in plasma and kidneys of 0-copy (68%, 77%) and 1-copy (61%, 64%) mice and IL-10 levels in 0-copy (80%, 78%) and 1-copy (47%, 25%) mice than 2-copy mice. A significant decrease in blood pressure occurred in rapamycin-treated 0-copy (19±4 mmHg) and 1-copy (12±3 mmHg) mice than untreated control mice. The results demonstrate that the expression of pro-inflammatory cytokines is greatly upregulated in Npr1 KO mice compared with 2-copy mice and rapamycin serves as the immune modulator of anti-inflammatory cytokines in these animals. The present findings implicate that rapamycin might act as an anti-inflammatory drug for the treatment of pathophysiology of hypertension-associated inflammation.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ananya Chatterjee ◽  
Subrata Chattopadhyay ◽  
Sandip K. Bandyopadhyay

Amla (Phyllanthus emblicaL.), apart from its food value, can be used as a gastroprotective agent in non steroidal anti-inflammatory drug (NSAID)-induced gastropathy. It has been suggested that the antioxidative property of amla is the key to its therapeutic effect. Hence, on the basis ofin vitroantioxidative potential, the ethanolic extract of amla (eAE) was selected forin vivostudy in NSAID-induced ulcer. Intriguingly, eAE showed biphasic activity in ulcerated mice, with healing effect observed at 60 mg/kg and an adverse effect at 120 mg/kg.The dose-dependent study revealed that switching from anti-oxidant to pro-oxidant shift and immunomodulatory property could be the major cause for its biphasic effect, as evident from the total antioxidant status, thiol concentration, lipid peroxidation, protein carbonyl content followed by mucin content, synthesis and cytokine status. Further, Buthionine sulfoxamine (BSO) pretreatment established the potential impact of antioxidative property in the healing action of eAE. However, eAE efficiently reduced pro-inflammatory cytokine (TNF- and IL-1) levels and appreciably upregulate anti-inflammatory cytokine (IL-10) concentration. In conclusion, gastric ulcer healing induced by eAE was driven in a dose-specific manner through the harmonization of the antioxidative property and modulation of anti-inflammatory cytokine level.


Sign in / Sign up

Export Citation Format

Share Document