scholarly journals A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria

2018 ◽  
Vol 69 (5) ◽  
pp. 820-828 ◽  
Author(s):  
Carlota Dobaño ◽  
Augusto J Nhabomba ◽  
Maria N Manaca ◽  
Tamara Berthoud ◽  
Ruth Aguilar ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Controlled Trial ◽  
Quantitative Polymerase Chain Reaction ◽  
Clinical Malaria ◽  
T Helper ◽  
Double Blind ◽  
Peripheral Blood Mononuclear ◽  
Malaria Exposure

Abstract Background The effect of timing of exposure to first Plasmodium falciparum infections during early childhood on the induction of innate and adaptive cytokine responses and their contribution to the development of clinical malaria immunity is not well established. Methods As part of a double-blind, randomized, placebo-controlled trial in Mozambique using monthly chemoprophylaxis with sulfadoxine-pyrimethamine plus artesunate to selectively control timing of malaria exposure during infancy, peripheral blood mononuclear cells collected from participants at age 2.5, 5.5, 10.5, 15, and 24 months were stimulated ex vivo with parasite schizont and erythrocyte lysates. Cytokine messenger RNA expressed in cell pellets and proteins secreted in supernatants were quantified by reverse-transcription quantitative polymerase chain reaction and multiplex flow cytometry, respectively. Children were followed up for clinical malaria from birth until 4 years of age. Results Higher proinflammatory (interleukin [IL] 1, IL-6, tumor necrosis factor) and regulatory (IL-10) cytokine concentrations during the second year of life were associated with reduced incidence of clinical malaria up to 4 years of age, adjusting by chemoprophylaxis and prior malaria exposure. Significantly lower concentrations of antigen-specific T-helper 1 (IL-2, IL-12, interferon-γ) and T-helper 2 (IL-4, IL-5) cytokines by 2 years of age were measured in children undergoing chemoprophylaxis compared to children receiving placebo (P < .03). Conclusions Selective chemoprophylaxis altering early natural exposure to malaria blood stage antigens during infancy had a significant effect on T-helper lymphocyte cytokine production >1 year later. Importantly, a balanced proinflammatory and anti-inflammatory cytokine signature, probably by innate cells, around age 2 years was associated with protective clinical immunity during childhood. Clinical Trials Registration NCT00231452.

scholarly journals Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial

2019 ◽  
Vol 59 (6) ◽  
pp. 2641-2649 ◽  
Author(s):  
Yusuke Tanaka ◽  
Yoshitaka Hirose ◽  
Yoshihiro Yamamoto ◽  
Yasunobu Yoshikai ◽  
Shinji Murosaki
Keyword(s):  
Lipid Metabolism ◽  
Lactobacillus Plantarum ◽  
Mononuclear Cells ◽  
Controlled Trial ◽  
Low Density Lipoprotein ◽  
Daily Intake ◽  
Density Lipoprotein ◽  
Control Group ◽  
Double Blind ◽  
Peripheral Blood Mononuclear

Abstract Purpose The effects of heat-killed Lactobacillus plantarum L-137 (HK L-137) on inflammation and lipid metabolism were investigated in overweight volunteers. Methods One hundred healthy subjects with a body mass index from 23.0 to 29.9 (51 men and 49 women; mean age: 41.4 years) were enrolled in this randomized, double-blind, placebo-controlled, parallel group study. Subjects were randomly assigned to daily administration of a tablet containing HK L-137 (10 mg) or a placebo tablet for 12 weeks. Blood samples were collected every 4 weeks to measure biomarkers of lipid metabolism and inflammatory mediators. Results The percent change of concanavalin A-induced proliferation of peripheral blood mononuclear cells was significantly larger in the HK L-137 group than in the control group, similar to previous studies. The decreases of aspartate aminotransferase and alanine aminotransferase over time were significantly larger in the HK L-137 group than in the control group, as were the decreases of total cholesterol, low-density lipoprotein cholesterol, and the leukocyte count at one time point. These effects of HK L-137 were stronger in the subjects with higher C-reactive protein levels. Conclusions These findings suggest that daily intake of HK L-137 can improve inflammation and lipid metabolism in subjects at risk of inflammation.

scholarly journals A Functional Virgin Olive Oil Enriched with Olive Oil and Thyme Phenolic Compounds Improves the Expression of Cholesterol Efflux-Related Genes: A Randomized, Crossover, Controlled Trial

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1732 ◽  
Author(s):  
Farràs ◽  
Arranz ◽  
Carrión ◽  
Subirana ◽  
Muñoz-Aguayo ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Olive Oil ◽  
Cholesterol Efflux ◽  
Mononuclear Cells ◽  
Controlled Trial ◽  
Virgin Olive Oil ◽  
Double Blind ◽  
Peripheral Blood Mononuclear ◽  
Chain Reactions ◽  
Control Intervention

The consumption of antioxidant-rich foods such as virgin olive oil (VOO) promotes high-density lipoprotein (HDL) anti-atherogenic capacities. Intake of functional VOOs (enriched with olive/thyme phenolic compounds (PCs)) also improves HDL functions, but the gene expression changes behind these benefits are not fully understood. Our aim was to determine whether these functional VOOs could enhance the expression of cholesterol efflux-related genes. In a randomized, double-blind, crossover, controlled trial, 22 hypercholesterolemic subjects ingested for three weeks 25 mL/day of: (1) a functional VOO enriched with olive oil PCs (500 mg/kg); (2) a functional VOO enriched with olive oil (250 mg/kg) and thyme PCs (250 mg/kg; FVOOT), and; (3) a natural VOO (olive oil PCs: 80 mg/kg, control intervention). We assessed whether these interventions improved the expression of cholesterol efflux-related genes in peripheral blood mononuclear cells by quantitative reverse-transcription polymerase chain reactions. The FVOOT intervention upregulated the expression of CYP27A1 (P = 0.041 and P = 0.053, versus baseline and the control intervention, respectively), CAV1 (P = 0.070, versus the control intervention), and LXRβ, RXRα, and PPARβ/δ (P = 0.005, P = 0.005, and P = 0.038, respectively, relative to the baseline). The consumption of a functional VOO enriched with olive oil and thyme PCs enhanced the expression of key cholesterol efflux regulators, such as CYP27A1 and nuclear receptor-related genes.

Evaluation of the potential anti-allergic effects of heat-inactivated Lactobacillus paracasei V0151 in vitro, ex vivo, and in vivo

2015 ◽  
Vol 6 (5) ◽  
pp. 697-705 ◽  
Author(s):  
Y.W. Liu ◽  
T.Y. Fu ◽  
W.S. Peng ◽  
Y.H. Chen ◽  
Y.M. Cao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Lactobacillus Paracasei ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear

The efficacy of Lactobacillus paracasei V0151 (V0151), isolated from the faeces of a child, to modulate immune responses was investigated. In RAW 264.7 cells expressing an inducible nitric oxide synthase (iNOS)-directed luciferase gene, heat-inactivated V0151 stimulated iNOS expression followed by nitric oxide production. V0151 significantly elevated interferon gamma, interleukin (IL)-10, tumour necrosis factor alpha, and IL-1β production in human peripheral blood mononuclear cells. In splenocytes isolated from ovalbumin (OVA)-sensitised BALB/c mice treated with OVA and V0151 at different bacterium-to-cell ratios (1:1, 10:1, and 20:1) for 96 h, IL-2, IL-4, IL-5, and IL-13 production was dose-dependently downregulated, whereas IL-12 was dose-dependently upregulated. Collectively, our findings indicate that V0151 might regulate pro-inflammatory factors in macrophages and splenocytes. Furthermore, the T helper 1/T helper 2 (Th1/Th2) balance was also skewed toward Th1 dominance through the elevation of Th1 cytokine production.

Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment

2016 ◽  
Vol 23 (4) ◽  
pp. 567-576 ◽  
Author(s):  
Ulrike Bühler ◽  
Vinzenz Fleischer ◽  
Felix Luessi ◽  
Ayman Rezk ◽  
Patrick Belikan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Healthy Controls ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Helper Cells

Objective: Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity. Methods: Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients ( n = 33), untreated RRMS patients ( n = 13), and healthy controls ( n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients. Results: Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-γ+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed. Conclusion: Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug’s mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.

scholarly journals Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

2009 ◽  
Vol 15 (3) ◽  
pp. 329-336 ◽  
Author(s):  
SA Broadley ◽  
D Vanags ◽  
B Williams ◽  
B Johnson ◽  
D Feeney ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Phase Ii ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Double Blind ◽  
Extended Phase ◽  
Peripheral Blood Mononuclear ◽  
Chaperonin 10 ◽  
Magnetic Resonance Imaging Mri

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium-enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

scholarly journals Tolerability and Safety of a Nutritional Supplement with Potential as Adjuvant in Colorectal Cancer Therapy: A Randomized Trial in Healthy Volunteers

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2001 ◽  
Author(s):  
Marta Gómez de Cedrón ◽  
José Moises Laparra ◽  
Viviana Loria-Kohen ◽  
Susana Molina ◽  
Juan Moreno-Rubio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Healthy Volunteers ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Study Groups ◽  
Nutritional Supplement ◽  
Double Blind ◽  
Peripheral Blood Mononuclear ◽  
Molecular Effects

Bioactive supplements display relevant therapeutic properties when properly applied according to validated molecular effects. Our previous research efforts established the basis to develop a dietary supplement based on a Rosmarinus officinalis supercritical extract. This was enriched in phenolic diterpenes (RE) with proven properties against signaling pathways involved in colon tumorigenesis, and shark liver oil rich in alkylglycerols (AKG) as a bioactive lipid vehicle to improve RE bioavailability and synergize with the potential therapeutic action of the extract. Herein, we have investigated the tolerability and safety of the supplement and the biological and molecular effects from an immuno-nutritional perspective. Sixty healthy volunteers participated in a six week, double-blind, randomized parallel pilot study with two study arms: RE-AKG capsules (CR) and control capsules (CC). Mean age (±SD) of volunteers was 28.32 (±11.39) and 27.5 (±9.04) for the control and the study groups, respectively. Safety of the CR product consumption was confirmed by analyzing liver profile, vital constants, and oxidation markers (LDLox in blood and isoprostanes and thromboxanes in urine). The following were monitored: (1) the phenotyping of plasmatic leukocytes and the ex vivo response of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs); (2) expression of genes associated with immune-modulation, inflammation, oxidative stress, lipid metabolism, and tumorigenesis; and (3) the correlation of selected genetic variants (SNPs) with the differential responses among individuals. The lack of adverse effects on liver profile and oxidation markers, together with adequate tolerability and safe immunological adaptations, provide high-quality information for the potential use of CR as co-adjuvant of therapeutic strategies against colorectal cancer.

scholarly journals Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nan Xiao ◽  
Meng Nie ◽  
Huanhuan Pang ◽  
Bohong Wang ◽  
Jieli Hu ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Fatal Outcome ◽  
Organ Injury ◽  
Cytokine Release ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear

AbstractCytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.

scholarly journals Initiating antiretroviral treatment early in infancy has long-term benefits on the HIV reservoir in late childhood and adolescence

2021 ◽  
Author(s):  
Véronique Avettand-Fenoel ◽  
Jérôme Lechenadec ◽  
Mariama Sadjo Diallo ◽  
Marine Fillion ◽  
Adeline Melard ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ex Vivo ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Childhood And Adolescence ◽  
Older Children ◽  
Peripheral Blood Mononuclear ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Cart Initiation

Abstract Background Early combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study aims to compare HIV reservoirs in children (5-12 years) and adolescents (13-17 years) who started cART before 6 months (early (E-)group) or after 2 years old (late (L-)group). Methods The ANRS-EP59-CLEAC study prospectively enrolled 76 HIV-1 perinatally-infected patients who reached HIV-RNA<400 copies/mL less than 24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cells (PBMCs) stimulation. Results Total HIV-DNA levels were lower in early- than late-treated patients (Children: 2.14 vs 2.87 log cp/million PBMCs, p<0.0001; Adolescents: 2.25 vs 2.74log, p<0.0001). Low reservoir was independently associated with treatment precocity, protective HLA and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than the other patients (4 vs 54 months, p=0.03). In those with sustained virological control, transitional memory and effector memory CD4+T cells were less infected in the E-group than in the L-group (p=0.03 and 0.02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between the groups. Conclusions Early cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies.

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