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Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy.
Berin, MC, Grishin, A, Masilamani, M, Leung, DYM, Sicherer, SH, Jones, SM, Burks, AW, Henning, AK, Dawson, P, Grabowska, J, et al
The Journal of allergy and clinical immunology. 2018;(1):149-158.e8
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BACKGROUND Egg allergy is phenotypically heterogeneous. A subset of patients with egg allergy can tolerate egg in an extensively heated form. Inclusion of baked egg (BE) into the diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown. OBJECTIVES We sought to study egg-specific antibody, basophil, and T-cell responses in children with reactivity or tolerance to BE. METHODS All participants underwent double-blind, placebo-controlled challenges to BE, and those who tolerated BE were challenged with unheated egg white protein to confirm clinical egg reactivity. Laboratory studies included serum antibody measurements, basophil activation tests, and CD154-based detection of egg-responsive T cells by using flow cytometry. RESULTS Of the 129 children studied, BE-reactive participants had significantly greater levels of egg-, ovalbumin-, and ovomucoid-specific IgE; lower ratios of egg-specific IgG4/IgE; and increased basophil activation in response to egg. Among all participants, CD154-based profiling revealed egg-responsive T cells producing IL-4 and IL-13 but little IL-10 or IFN-γ, as well as the presence of egg-responsive Foxp3+CD25+CD127low regulatory T cells. Egg-responsive T cells expressed CCR4, CCR6, and CXCR5, indicating capacity for homing to the skin, mucosa, and B-cell follicles. However, neither the frequency nor phenotype of egg-responsive T cells was different in those with tolerance or reactivity to BE. CONCLUSIONS Egg-specific antibody and basophil responses, but not T-cell responses, are greater in those with reactivity versus tolerance to BE. Egg-specific antibody and T-cell responses were highly heterogeneous in this cohort. The clinical implications of this immune heterogeneity will need to be studied longitudinally.
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Effects of probiotics supplementation and circuit training on immune responses among sedentary young males.
Ibrahim, NS, Ooi, FK, Chen, CK, Muhamad, AS
The Journal of sports medicine and physical fitness. 2018;(7-8):1102-1109
Abstract
BACKGROUND Growing evidence suggests that probiotics may have positive benefits on immune responses following endurance exercise. However, little attention has been given to its possible beneficial effects on immune responses following resistance exercise. METHODS Forty-one healthy sedentary males were recruited and randomised into four groups: sedentary control with placebo (C), probiotics (P), circuit training with placebo (Ex), and circuit training with probiotics (PEx) groups. Participants in the Ex and PEx groups performed a progressive load of circuit training at 3 times/week for 12 weeks. Each circuit comprised 10 exercises with work to rest ratio of 1:2. Participants consumed either multi-strain probiotics or placebo twice daily for 12 weeks. Body height and weight, blood pressure, resting heart rate, saliva and blood samples were collected at pre- and post-tests. RESULTS Saliva flow rate and salivary IgA, α-amylase, lactoferrin and lysozyme responses were not significantly different (P>0.05) between groups and also between pre- and post-test within each group. Similarly, total leukocytes, total lymphocytes, T lymphocytes, T-helper, T-cytotoxic, B lymphocytes, and natural killer cells counts were not significantly affected (P>0.05) by the probiotics and/or circuit training. However, circuit training significantly increased (P<0.05) immune cells count at post-test as compared to pre-test. Yet, a combination of circuit training and probiotics showed no significant (P>0.05) effects on immune cells count. CONCLUSIONS This study did not provide enough support for the positive effects of probiotics on immune responses among sedentary young males following resistance exercise. However, 12 weeks of circuit training enhanced immune cells count.
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Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial.
Barnett, JB, Dao, MC, Hamer, DH, Kandel, R, Brandeis, G, Wu, D, Dallal, GE, Jacques, PF, Schreiber, R, Kong, E, et al
The American journal of clinical nutrition. 2016;(3):942-51
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BACKGROUND Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. DESIGN This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 μg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 μg serum Zn/dL failed to increase their serum zinc to ≥70 μg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.
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Aged Garlic Extract Modifies Human Immunity.
Percival, SS
The Journal of nutrition. 2016;(2):433S-436S
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Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification. The purpose of this review was to summarize the influence of aged garlic extract (AGE) on the immune system. The author's laboratory is interested in AGE's effects on cell proliferation and activation and inflammation and to learn whether those changes might affect the occurrence and severity of colds and flu. Healthy human participants (n = 120), between 21 and 50 y of age, were recruited for a randomized, double-blind, placebo-controlled parallel-intervention study to consume 2.56 g AGE/d or placebo supplements for 90 d during the cold and flu season. Peripheral blood mononuclear cells were isolated before and after consumption, and γδ-T and NK cell function was assessed by flow cytometry. The effect on cold and flu symptoms was determined by using daily diary records of self-reported illnesses. After 45 d of AGE consumption, γδ-T and NK cells proliferated better and were more activated than cells from the placebo group. After 90 d, although the number of illnesses was not significantly different, the AGE group showed reduced cold and flu severity, with a reduction in the number of symptoms, the number of days participants functioned suboptimally, and the number of work/school days missed. These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation. This trial was registered at clinicaltrials.gov as NCT01390116.
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Effects of zinc sulfate supplementation on cell-mediated immune response in head and neck cancer patients treated with radiation therapy.
Sangthawan, D, Phungrassami, T, Sinkitjarurnchai, W
Nutrition and cancer. 2015;(3):449-56
Abstract
Zinc deficiency is an important factor that impairs cellular immunity and contributes to low T lymphocyte counts in head and neck cancers. Persistent T lymphopenia is clinically relevant in terms of tumor persistence and/or recurrence. The primary objective was to evaluate the impact of zinc sulfate supplementation on the absolute numbers of circulating T lymphocytes and T lymphocyte subpopulations. The secondary objectives were to evaluate overall survival, progression-free survival, and the adverse events of zinc sulfate. Seventy-two head and neck cancer patients were enrolled in a randomized, double-blind, placebo-controlled trial. Zinc sulfate 50 mg in 10 cc and an identically appearing placebo were self-administered 3 times daily at meal times. Blood samples were obtained for complete blood count, total T lymphocytes and T lymphocyte subpopulations before radiation therapy as baselines, at the fifth week during radiation therapy, and at the first month after completion of radiation therapy. The baseline characteristics of patients, tumors, and treatments and the baseline lymphocyte parameters were not significantly different between the 2 groups. Zinc sulfate supplementation during head and neck radiation therapy showed no increase in absolute numbers of circulating T lymphocytes, T lymphocyte subpopulations, or survival with acceptable side effects.
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Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients.
D'Amelio, P, Sassi, F, Buondonno, I, Fornelli, G, Spertino, E, D'Amico, L, Marchetti, M, Lucchiari, M, Roato, I, Isaia, GC
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2015;(12):2785-91
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UNLABELLED We evaluated the effect of parathyroid hormone (PTH) on Wnt10b production by immune system cells in humans. We showed that bone anabolic effect of intermittent PTH treatment may be amplified by T cells through increased production of Wnt10b. Chronic increase in PTH as in primary hyperparathyroidism does not increase Wnt10b expression. INTRODUCTION The aim of this study is to assess the effect of PTH on Wnt10b production by immune system cells in humans. We assessed both the effect of intermittent PTH administration (iPTH) and of chronic PTH hypersecretion in primary hyperparathyroidism (PHP). METHODS Eighty-two women affected by post-menopausal osteoporosis were randomly assigned to treatment with calcium and vitamin D alone (22) or plus 1-84 PTH (42), or intravenous ibandronate (18). Wnt10b production by unfractioned blood nucleated cells and by T, B cells and monocytes was assessed by real-time RT-PCR and ELISA at baseline, 3, 6, 12 and 18 months of treatment. The effect of chronic elevation of PTH was evaluated in 20 patients affected by PHP at diagnosis and after surgical removal of parathyroid adenoma. WNT10b from both osteoporotic and PHP patients was compared to healthy subjects matched for age and sex. RESULTS iPTH increases Wnt10b production by T cells, whereas PHP does not. After surgical restoration of normal parathyroid function, WNT10b decreases, although it is still comparable with healthy subjects' level. Thus, chronic elevation of PTH does not significantly increase WNT10b production as respect to control. CONCLUSIONS This is the first work showing the effect of both intermittent and chronic PTH increase on Wnt10b production by immune system cells. We suggest that, in humans, T cells amplified the anabolic effect of PTH on bone, by increasing Wnt10b production, which stimulates osteoblast activity.
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A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans.
Charron, CS, Dawson, HD, Albaugh, GP, Solverson, PM, Vinyard, BT, Solano-Aguilar, GI, Molokin, A, Novotny, JA
The Journal of nutrition. 2015;(11):2448-55
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BACKGROUND Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. OBJECTIVE We designed a study to probe the mechanisms of garlic action in humans. METHODS We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. RESULTS The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P < 0.05). The mRNA levels of 5 of the 7 genes that were upregulated in the human trial were also upregulated in cell culture at 3 and 6 h: AHR, HIF1A, JUN, OSM, and REL. Fold-increases in mRNA transcripts in cell culture ranged from 1.7 (HIF1A) to 12.1 (JUN) (P < 0.01). OSM protein was measured by ELISA and was significantly higher than the control at 3, 6, and 24 h (24 h: 19.5 ± 1.4 and 74.8 ± 1.4 pg/mL for control and garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. CONCLUSION These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591.
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Influence of the slow infusion of a soybean oil emulsion on plasma cytokines and ex vivo T cell proliferation after an esophagectomy.
Kagawa, Y, Maeda, T, Kato, Y, Ueda, I, Kudo, T, Watanabe, N, Kimura, M, Minami, S, Sakamoto, T, Yamada, H, et al
JPEN. Journal of parenteral and enteral nutrition. 2013;(1):123-8
Abstract
BACKGROUND Lipid emulsions have been suggested to reduce immune responses, particularly in severely stressed patients. The authors investigated the influence of the slow intravenous infusion of a soybean oil-based lipid emulsion on some immune parameters in patients who had undergone an esophagectomy for esophageal cancer. METHODS Thirty-two patients who had undergone an esophagectomy were randomly divided into a lipid emulsion (LPD)-treated group and a control group. All patients received parenteral feeding with a glucose-based solution. Patients in the LPD group received 100 mL of a 20% soybean oil emulsion for 7 days after the esophagectomy in addition to the glucose-based feeding. A slow infusion rate (0.09-0.12 g/kg/h) was adopted to take account of the intrinsic degradation of infused lipids. Immune responses were measured based on lymphocyte proliferation and serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The authors also measured levels of rapid turnover proteins (ie, transferrin, prealbumin, and retinol-binding protein). RESULTS Phytohemagglutinin- and concanavalin A-stimulated lymphocyte proliferation significantly decreased after the esophagectomy, but no significant difference was seen between the LPD and control groups. No significant difference in changes in plasma concentrations of MCP-1, IL-6 and TNF-α occurred between the 2 groups either. Plasma concentrations of rapid turnover proteins did not differ between the groups. CONCLUSIONS These results indicate that the lipid emulsion did not affect the immune parameters measured in patients who had undergone an esophagectomy when administered at a slow rate.
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Cholecalciferol supplementation in HIV-infected youth with vitamin D insufficiency: effects on vitamin D status and T-cell phenotype: a randomized controlled trial.
Giacomet, V, Vigano, A, Manfredini, V, Cerini, C, Bedogni, G, Mora, S, Borelli, M, Trabattoni, D, Zuccotti, GV
HIV clinical trials. 2013;(2):51-60
Abstract
OBJECTIVES In addition to its known effects on bone metabolism, vitamin D may regulate immune function. DESIGN We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and affect the T-cell phenotype in HIV-infected youth with vitamin D insufficiency. METHODS Fifty-two HIV-infected patients aged 8 to 26 years and with serum 25(OH) D <30 ng/mL were randomized to receive orally vitamin D3 100,000 IU or placebo every 3 months for 4 doses. Serum 25(OH)D, 1,25(OH)2D, PTH, and CD4+ T cells were assessed 3 months before baseline and at 0, 3, 6, 9, and 12 months, while Th1-, Th2-, Th17-, and Treg-subsets and T-lymphocyte vitamin D receptor were assessed at 0, 3, and 12 months. RESULTS Forty-eight subjects (25 receiving vitamin D and 23 receiving placebo) completed the RCT. Cholecalciferol supplementation produced an early (3 months) decrease in PTH, a concomitant increase in 25(OH)D, and a later (6 months) increase in 1,25(OH)2D levels, all persisting at 12 months. The frequency of vitamin D insufficiency at 12 months was 20% versus 60% in the intervention versus placebo group (P = .007). Cholecalciferol supplementation had no effect on CD4+ T-cell counts but was associated with a decreased Th17:Treg ratio at 3 months. CONCLUSIONS In our cohort of HIV-infected youth, a 12-month cholecalciferol supplementation increased 25(OH)D and 1-25(OH)2D and decreased PTH levels but had no effect on CD4+ T-cells. However, it was associated with changes in CD4+ T-cell phenotype, warranting further investigation.
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Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 modulate gene expression of subset specific transcription factors and cytokines in peripheral blood mononuclear cells of obese and overweight people.
Zarrati, M, Shidfar, F, Nourijelyani, K, Mofid, V, Hossein zadeh-Attar, MJ, Bidad, K, Najafi, F, Gheflati, Z, Chamari, M, Salehi, E
BioFactors (Oxford, England). 2013;(6):633-43
Abstract
Probiotics are believed to have interaction with immune cells through sustained effects on gene expression of different cytokines and transcription factors. The present randomized doubled-blind controlled clinical trial was performed recruiting 75 individuals with BMI 25-35, who were randomly assigned to the following three groups: Group 1 (n = 25) who consumed regular yogurt as part of a low calorie diet [RLCD], group 2 (n = 25) who received probiotic yogurt with a LCD [PLCD] and group 3 (n = 25) who consumed probiotic yogurt without LCD [PWLCD] for 8 week. Participants in PLCD and PWLCD groups received 200 g/day yogurt containing Lactobacillus acidophilus La5, Bifidobacterium Bb12, and lactobacillus casei DN001 10(8) cfu/gr. The expression of the FOXP3, T-bet, GATA3, TNF-α, IFN-γ, TGF-β, and ROR-γt in PBMCs genes were assessed, before and after intervention. In three groups, ROR-γt expression was reduced (P = 0.007) and FOXP3 was increased (P < 0.001). The expression of TNFα, TGFβ, and GATA3 genes did not change among all groups after intervention. Interestingly, the expression of T-bet gene, which was significantly decreased in PLCD and PWLCD groups (P < 0.001), whereas gene expression of IFN-γ decreased in all three groups. Our results suggest that weight loss diet and probiotic yogurt had synergistic effects on T-cell subset specific gene expression in peripheral blood mononuclear cells among overweight and obese individuals.