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Four weeks of spice consumption lowers plasma proinflammatory cytokines and alters the function of monocytes in adults at risk of cardiometabolic disease: secondary outcome analysis in a 3-period, randomized, crossover, controlled feeding trial.
Oh, ES, Petersen, KS, Kris-Etherton, PM, Rogers, CJ
The American journal of clinical nutrition. 2022;(1):61-72
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Abstract
BACKGROUND Numerous studies demonstrate acute anti-inflammatory properties of individual spices, but none have examined the effect of longer-term consumption of a spice blend incorporated in a meal. OBJECTIVES We investigated the effect of longer-term spice consumption on inflammatory cytokines and monocyte subsets [classical (CM), intermediate (IM), nonclassical (NCM)] in adults at risk of cardiometabolic disease. METHODS A 3-period, randomized, crossover, controlled feeding trial was conducted. Participants (n = 71 recruited; n = 63 completed) randomly consumed diets differing in terms of the quantity of spices: 0.547 g (low-dose spice diet; LSD), 3.285 g (medium-dose spice diet; MSD), or 6.571 g (high-dose spice diet; HSD) · d-1 · 2100 kcal-1, for 4 wk with a ≥2-wk washout between diets. At baseline and after each diet period, proinflammatory cytokines (IL-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and TNF-α) in plasma and LPS-stimulated peripheral blood mononuclear cell culture supernatants, and the phenotype and function of monocyte subsets, were measured in fasted participants. Postprandial proinflammatory cytokines also were quantified at baseline by consumption of a low-spice-dose test meal, and after each diet period by consumption of a test meal containing a spice dose corresponding to daily spice consumption during the preceding 4-wk diet period. RESULTS Fasting plasma IL-6 was reduced (mean ± SEM: -118.26 ± 50.63 fg/mL; P < 0.05) after MSD compared with baseline. Postprandial plasma IL-1β, IL-8, and TNF-α were lower (mean ± SEM -9.47 ± 2.70 fg/mL, -0.20 ± 0.05 pg/mL, and -33.28 ± 12.35 fg/mL, respectively) after MSD compared with LSD (main diet effect; P < 0.05). CM adherence was reduced (mean ± SEM: -0.86 ± 0.34; P = 0.034) after HSD compared with LSD. IM migration was reduced after MSD and HSD compared with LSD (mean ± SEM: -0.39 ± 0.09 and -0.56 ± 0.14, respectively; P < 0.05). CONCLUSIONS Four weeks of MSD consumption reduced fasting plasma IL-6 and postprandial plasma IL-1β, IL-8, and TNF-α as well as altering monocyte function.This trial was registered at clinicaltrials.gov as NCT03064932.
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The effect of moderate wine consumption on cytokine secretion by peripheral blood mononuclear cells: A randomized clinical study in coronary heart disease patients.
Fragopoulou, E, Argyrou, C, Detopoulou, M, Tsitsou, S, Seremeti, S, Yannakoulia, M, Antonopoulou, S, Kolovou, G, Kalogeropoulos, P
Cytokine. 2021;:155629
Abstract
Many studies conclude that wine consumption is related to lower risk for cardiovascular diseases partially through the amelioration of inflammatory biomarkers. The aim of the present study was to examine the effects of wine consumption on the inflammatory response and to compare these effects with the consumption of similar amount of alcohol without the wine micro-constituents in cardiovascular disease patients. Therefore, a randomized, single-blind, controlled, three-arm parallel intervention study was designed. Cardiovascular disease patients were randomly assigned to one of the three groups. In Group A participants consumed no alcohol, in Group B (ethanol group) and Group C (wine group) participants consumed 27 g of alcohol per day. Biological samples were collected at the beginning, on the 4th and 8th week and several biomarkers were measured. Peripheral blood mononuclear cells that were isolated from patients were incubated under basal and inflammatory conditions for 4 and 24 h and the secretion of interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) was measured. No significant difference was observed among the three groups before the initiation or during the intervention in the most soluble biomarkers. Higher TNFα secretion by peripheral blood mononuclear cells was observed at basal conditions in the ethanol group both at 4 and 24 h of incubation versus baseline secretion. Furthermore, lower secretion of the ΤNFα was observed after 8 weeks of intake in the wine group versus the ethanol group, both at 4 and 24 h of incubation. In conclusion, the light to moderate wine consumption for 8 weeks revealed an attenuation of the ethanol consumption effect on cytokine secretion at basal conditions from the patients' peripheral blood mononuclear cells.
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Daily apple consumption reduces plasma and peripheral blood mononuclear cell-secreted inflammatory biomarkers in adults with overweight and obesity: a 6-week randomized, controlled, parallel-arm trial.
Liddle, DM, Lin, X, Cox, LC, Ward, EM, Ansari, R, Wright, AJ, Robinson, LE
The American journal of clinical nutrition. 2021;(2):752-763
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Abstract
BACKGROUND Obesity-associated low-grade inflammation contributes to the development of cardiovascular disease (CVD). Apples are rich in anti-inflammatory bioactives including polyphenols and fiber. OBJECTIVES We aimed to determine the effects of regular apple consumption on fasting plasma biomarkers of inflammation (primary outcome), endotoxemia, carbohydrate and lipid metabolism (glucose, insulin, triacylglycerol; secondary outcomes), and peripheral blood mononuclear cell (PBMC)-secreted cytokines (secondary outcome) in individuals with overweight and obesity. METHODS A randomized, controlled, parallel-arm trial was conducted with n = 46 participants. After avoiding foods and beverages rich in polyphenols and fiber for 2 wk, participants consumed 3 whole Gala apples (∼200 g edible parts)/d as part of their habitual diet (n = 23) or avoided apples (control, n = 23) for 6 wk. All participants limited consumption of polyphenols and fiber during the 6-wk trial. Fasting blood samples were collected before and after 6 wk for analysis of plasma biomarkers and isolation of PBMCs, which were cultured for 24 h unstimulated or stimulated with LPS (10 ng/mL). RESULTS Forty-four participants completed the trial (30 female, 14 male; mean ± SEM age: 45.4 ± 2.2 y; BMI: 33.4 ± 0.9 kg/m2). After ANCOVA and correcting for multiple comparisons, apples decreased fasting plasma C-reactive protein by 17.0% (range: 14.3%-19.6%, P = 0.005), IL-6 by 12.4% (range: 6.7%-17.5%, P < 0.001), and LPS-binding protein by 20.7% (range: 14.1%-26.4%, P < 0.001) compared with control. Apples also decreased PBMC-secreted IL-6 by 28.3% (range: 22.4%-33.5%, P < 0.001) and IL-17 by 11.0% (range 5.8-15.6%, P = 0.003) in the unstimulated condition compared with control. Exploratory analysis showed apples also increased plasma total antioxidant capacity by 9.6% (range: 1.7-18.9%, P = 0.002) compared with control. However, apples had no effect on anthropometric or other CVD risk markers. CONCLUSIONS Six-week daily whole Gala apple consumption may be an effective dietary strategy to mitigate the obesity-associated inflammation that exacerbates CVD risk, without weight loss. This trial was registered at clinicaltrials.gov as NCT03523403.
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Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study.
Juncal-Ruiz, M, Riesco-Davila, L, Vazquez-Bourgon, J, Ortiz-Garcia de la Foz, V, Mayoral-Van Son, J, Ayesa-Arriola, R, Setien-Suero, E, Leza, JC, Lopez-Hoyos, M, Crespo-Facorro, B
International journal of molecular sciences. 2020;(17)
Abstract
Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1-9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1-9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-α) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.
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Intake of Fermented Dairy Products Induces a Less Pro-Inflammatory Postprandial Peripheral Blood Mononuclear Cell Gene Expression Response than Non-Fermented Dairy Products: A Randomized Controlled Cross-Over Trial.
Rundblad, A, Holven, KB, Øyri, LKL, Hansson, P, Ivan, IH, Gjevestad, GO, Thoresen, M, Ulven, SM
Molecular nutrition & food research. 2020;(21):e2000319
Abstract
SCOPE It is aimed to investigate how intake of high-fat meals composed of different dairy products with a similar fat content affects postprandial peripheral blood mononuclear cell (PBMC) expression of inflammation-related genes, as well as circulating inflammatory markers and metabolites. METHODS AND RESULTS Healthy subjects (n = 47) consume four different high-fat meals composed of either butter, cheese, whipped cream, or sour cream in a randomized controlled cross-over study. Fasting and postprandial PBMC gene expression, plasma metabolites, and circulating inflammatory markers are measured. Using a linear mixed model, it is found that expression of genes related to lymphocyte activation, cytokine signaling, chemokine signaling, and cell adhesion is differentially altered between the four meals. In general, intake of the fermented products cheese and sour cream reduces, while intake of the non-fermented products butter and whipped cream increases, expression of these genes. Plasma amino acid concentrations increase after intake of cheese compared to the other meals, and the amino acid changes correlate with several of the differentially altered genes. CONCLUSION Intake of fermented dairy products, especially cheese, induces a less inflammatory postprandial PBMC gene expression response than non-fermented dairy products. These findings may partly explain inconsistent findings in studies on health effects of dairy products.
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Decrease of Perforin Expressing Lymphocytes after On-Pump Coronary Artery Bypass Grafting Surgery Irrespective of Carbohydrate Preoperative Oral Feeding.
Sokolic, J, Knezevic, D, Kuharic, J, Medved, I, Sustic, A, Zupan, Z, Laskarin, G, Tadin, T, Sotošek Tokmadžić, V
The heart surgery forum. 2019;(3):E218-E224
Abstract
BACKGROUND Coronary artery bypass grafting (CABG) surgery continues to be the gold standard for treating the patients with coronary artery disease. CABG surgery can be performed on or off cardiopulmonary bypass, termed as on-pump or off-pump CABG, respectively. It has been shown that CABG surgery, preferably on-pump CABG surgery, leads to the changes of cell immunity during perioperative and early postoperative period. The mechanisms of regulation of the immune response in patients during and early after surgical revascularization are not fully understood. The aim of this study was to investigate the influence of carbohydrate preoperative oral feeding on frequency and perforin expression in peripheral blood lymphocytes in patients after on- or off-pump CABG surgery in early postoperative period. PATIENTS AND METHODS In this prospective clinical study, 80 patients scheduled for CABG surgery were included in the study. The patients were randomly allocated into four groups (20 in each group): patients in Group 1 underwent on-pump CABG and did not receive carbohydrate preoperative oral feeding; patients in Group 2 underwent on-pump CABG and were preoperatively fed; patients in Group 3 underwent off-pump CABG and did not receive carbohydrate preoperative oral feeding; while patients in Group 4 underwent off-pump CABG and received carbohydrate preoperative oral feeding. Blood samples were collected immediately before (T1), 24 (T2) and 72 (T3) hours after the surgery. Peripheral blood mononuclear cells were isolated by gradient centrifugation and simultaneously labelled by antigens using fluorochrome-conjugated monoclonal antibodies. Frequency of T lymphocytes, NK and NKT cells, their subsets as well as their perforin expression were detected, and analyzed by flow cytometry. RESULTS There was significant decrease in frequency of CD3+ and CD3+CD4+ cells, as well as perforin expressing CD3+CD8+ cells in patients who underwent on-pump CABG in comparison to patients who underwent off-pump CABG 24 hours after the surgery. Carbohydrate preoperative oral feeding did not effect changes in lymphocytes subpopulations and perforin expression at any time point. CONCLUSION Decreases of CD3+ cells on account of CD3+CD4+ subsets, and perforin expressing cells on account of CD3+CD8+ perforin+ cells were found in patients who had undergone on-pump CABG, but not in patients who had undergone off-pump CABG surgery, irrespectively of carbohydrate preoperative oral feeding.
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The effect of retinyl-palmitate on the level of pro and anti-inflammatory cytokines in multiple sclerosis patients: A randomized double blind clinical trial.
Bitarafan, S, Mohammadpour, Z, Jafarirad, S, Harirchian, MH, Yekaninejad, MS, Saboor-Yaraghi, AA
Clinical neurology and neurosurgery. 2019;:101-105
Abstract
OBJECTIVE Multiple sclerosis (MS) is an inflammatory and autoimmune disease associated with the imbalance of cytokines secreted from CD4+ T cells. Studies have shown that vitamin A and its active derivatives are able to modulate the immune system in MS patients. The aim of the present study was to investigate the effect of supplementation of retinyl palmitate (RP), the dietary form of vitamin A, on pro- and anti-inflammatory cytokines in the plasma and supernatants of cultured peripheral blood mononuclear cells (PBMCs) of MS patients. PATIENTS AND METHODS Thirty-six relapsing-remitting MS patients were enrolled in this double-blind randomized clinical trial. Participants received one capsule of 25,000 IU RP or a placebo per day for six months. Blood samples were taken before and after intervention. After intervention, the PBMCs were isolated and cultured. The levels of pro- and anti-inflammatory cytokines in the plasma and supernatant of cells stimulated with myelin oligodendrocyte glycoprotein, phytohemagglutinin or vehicle (media) were determined. The sample t-test and Mann Whitney U test were used to compare data between groups. RESULTS The changes in pro-inflammatory cytokine levels (IL-1β, TNF-α, IFN- γ, IL-2, IL-6, and IL-17) in the serum and supernatant of MS patients were not significant (p > 0.05). There were also no significant changes in the levels of anti-inflammatory cytokines (IL-10, IL-13, IL-4, and TGF-β) (p > 0.05). CONCLUSION Unexpectedly, this study found no significant changes in cytokine levels after six months of RP supplementation in MS patients. The results of other studies by our team have shown significant changes in the gene expression of the cytokines in response to RP supplements. Therefore, we recommend that periodic follow-up of RP supplementation may be needed to reveal changes in the level of the cytokines in the plasma and PBMCs and to clarify the real effect of RP on the immune factor levels in the serum of MS patients.
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Pomegranate Juice Increases Sirtuin1 Protein in Peripheral Blood Mononuclear Cell from Patients with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trial.
Sohrab, G, Nasrollahzadeh, J, Tohidi, M, Zand, H, Nikpayam, O
Metabolic syndrome and related disorders. 2018;(8):446-451
Abstract
BACKGROUND Few studies have examined anti-inflammatory effects of pomegranate juice (PJ). The present study aimed to evaluate the effect of PJ on nuclear factor kappa B (NF-κB) p65 and sirtuin1 in peripheral blood mononuclear cell (PBMC), and plasma vascular inflammation biomarkers. METHODS Patients with type 2 diabetes were randomly assigned to either the PJ (n = 22) or the placebo group (n = 22). The patients in the PJ group received 250 mL of PJ daily for 12 weeks, whereas the placebo group received corresponding control beverages of similar color and energy content. At baseline and at the end of week 12, fasting plasma concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and soluble E-selectin (sE-selectin) were measured. NF-κB p65 and SIRT1 were measured in the PBMC. RESULTS Plasma sE-selectin concentration decreased significantly in the PJ group at the end of week 12 compared to baseline (P < 0.001 for treatment effect), and the reduction was significant in comparison with the placebo group (P < 0.05 for treatment effect). There were no significant differences between the two groups in plasma sICAM-1 and sVCAM-1. At the end of the study, compared with the placebo group, NF-κB p65 in PBMC was significantly lower (P < 0.01 for treatment effect) and SIRT1 was significantly higher (P < 0.0001 for treatment effect) in the PJ group. CONCLUSION This study supports the PJ consumption as a food with potential benefits in individuals with type 2 diabetes as evidenced by improvements in NF-κB and SIRT1 levels in PBMC of study participants.
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Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study.
Zambrano, T, Hirata, RDC, Hirata, MH, Cerda, Á, Salazar, LA
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2018;:55-61
Abstract
AIM: Although statins are considered a cornerstone for the treatment of high cholesterol levels due to their powerful cholesterol-lowering effects, response to drug administration is still one of the main pitfalls of statin treatment. So far, the reasons underlying this undesired outcome are still poorly understood, but recently, various studies have suggested that miRNAs may be involved. Therefore, we aimed at evaluating the effect of short-term low-dose treatment with 2 statins on miRNAs expression in patients with hypercholesterolemia. METHODS A total of 40 hypercholesterolemic (HC) subjects following 1 month of atorvastatin (10 mg/day; n = 20) or simvastatin (10 mg/day; n = 20) were included. Multiple available boinformatic algorithms (TargetScan, miRanda, DianaLab, MicroCosm and PicTar) were employed to select miRNAs regulating genes involved in cholesterol metabolism and statin response. Differential miRNAs expression was determined in peripheral cells using the miScript® miRNA PCR Array platform. Pathways involving differentially expressed miRNAs were explored using the Ingenuity Pathway Analysis software. RESULTS Atorvastatin repressed miR-29a-3p, miR-29b-3p, miR-300, miR-33a-5p, miR-33b-5p and miR-454-3p in HC subjects. On the contrary, simvastatin did not show any effect on miRNAs expression. Network analysis indicated that atorvastatin-modulated miRNAs regulate key cholesterol genes (ABCA1, HMGCR, INSIG1, LDLR, LPL, SCAP and SREBF1). Further subgroups analyses showed that miR-106b-5p, miR-17-3p and miR-590-5p were repressed in HC subjects within the lower quartile of atorvastatin response (lower LDL-C reduction), while the expression of miR-106b-5p, miR-17-3p and miR-183-5p was higher in the upper quartile of simvastatin response (higher LDL-C reduction) (p < 0.05). CONCLUSION We show that a miRNAs-mediated epigenetic mechanism is differentially affected by statins therapy in vivo, which could be implicated in the variable response to these drugs. Further studies are necessary to disclose their particular role in the cholesterol-reduction response to statins.
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DNA methylation signatures in peripheral blood mononuclear cells from a lifestyle intervention for women at midlife: a pilot randomized controlled trial.
McEwen, LM, Gatev, EG, Jones, MJ, MacIsaac, JL, McAllister, MM, Goulding, RE, Madden, KM, Dawes, MG, Kobor, MS, Ashe, MC
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(3):233-239
Abstract
Physical activity confers many health benefits, but the underlying mechanisms require further exploration. In this pilot randomized controlled trial we tested the association between longitudinal measures of DNA methylation and changes in objective measures, including physical activity, weight loss, and C-reactive protein levels in community-dwelling women aged 55 to 70 years. We assessed DNA methylation from 20 healthy postmenopausal women, who did not have a mobility disability and allocated them to a group-based intervention, Everyday Activity Supports You, or a control group (monthly group-based health-related education sessions). The original randomized controlled trial was 6 months in duration and consisted of nine 2-h sessions that focused on reducing sedentary behaviour for the intervention group, or six 1-h sessions that focused on other topics for the control group. We collected peripheral blood mononuclear cells, both at baseline and 6 months later. Samples were processed using the Illumina 450k Methylation array to quantify DNA methylation at >485 000 CpG sites in the genome. There were no significant associations between DNA methylation and physical activity, but we did observe alterations at epigenetic modifications that correlated with change in percent body weight over a 6-month period at 12 genomic loci, 2 of which were located near the previously reported weight-associated genes RUNX3 and NAMPT. We also generated a potential epigenetic predictor of weight loss using baseline DNA methylation at 5 CpG sites. These exploratory findings suggest a potential biological link between body weight changes and epigenetic processes.