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1.
The Effects of a Gluten-Free Diet on Immune Markers and Kynurenic Acid Pathway Metabolites in Patients With Schizophrenia Positive for Antigliadin Antibodies Immunoglobulin G.
Friendshuh, CR, Pocivavsek, A, Demyonovich, H, Rodriguez, KM, Cihakova, D, Talor, MV, Richardson, CM, Vyas, G, Adams, HA, Baratta, AB, et al
Journal of clinical psychopharmacology. 2020;(3):317-319
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2.
Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial.
Wolf, GT, Liu, S, Bellile, E, Sartor, M, Rozek, L, Thomas, D, Nguyen, A, Zarins, K, McHugh, JB, ,
Oral oncology. 2020;:104928
Abstract
OBJECTIVES IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). METHODS A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR). RESULTS Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). CONCLUSIONS The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT02609386).
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3.
Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease.
Goel, G, Tye-Din, JA, Qiao, SW, Russell, AK, Mayassi, T, Ciszewski, C, Sarna, VK, Wang, S, Goldstein, KE, Dzuris, JL, et al
Science advances. 2019;(8):eaaw7756
Abstract
Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4+ T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.
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4.
Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebo-controlled trial.
Sharifi, A, Vahedi, H, Nedjat, S, Rafiei, H, Hosseinzadeh-Attar, MJ
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2019;(10):681-687
Abstract
Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon. It has been proposed that the UC pathogenesis may be related to vitamin D deficiency and/or vitamin D administration in UC patients may have an ameliorating effect on the intestinal inflammation. The aim of this study was to assess the effect of vitamin D on the serum levels of immune cytokines in UC patients. In this double-blind randomized controlled trial, 90 mild-to-moderate UC patients were assigned to get either a single muscular injection of 7.5 mg vitamin D3 or 1 mL normal saline as placebo. Three months later serum levels of IL-4, IL-10, IL-12p70, IFN-γ, and TNF-α were measured. Two group variables were compared using independent t-test and analysis of covariance (ANCOVA). There was a significant increase in vitamin D only in the vitamin D group. Compared to placebo, vitamin D had significant decreasing effects on serum TNF-α, IFN-γ, and IL12p70 levels, but it had no significant effect on serum levels of IL4 and IL10. Vitamin D seems to inhibit Th1 immune responses and have no effect on Th2 responses. The findings of this study support several in vitro studies, which suggest a therapeutic immunomodulatory potential of vitamin D.
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5.
No detectable effects of acute tryptophan depletion on short-term immune system cytokine levels in healthy adults.
Hildebrandt, CS, Helmbold, K, Linden, M, Langen, KJ, Filss, CP, Runions, KC, Stewart, RM, Rao, P, Moore, JK, Mahfouda, S, et al
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2019;(5):416-423
Abstract
Objectives: Recent research suggested an influence of diminished central nervous serotonin (5-HT) synthesis on the leptin axis via immunological mechanisms in healthy adult females. However, studies assessing immunological parameters in combination with dietary challenge techniques that impact brain 5-HT synthesis in humans are lacking. Methods: In the present trial, a pilot analysis was conducted on data obtained in healthy adult humans receiving either different dietary acute tryptophan depletion (ATD) challenge or tryptophan (TRP)-balanced control conditions (BAL) to study the effects of reduced central nervous 5-HT synthesis on serum tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 concentrations. The data of N = 35 healthy adults were analysed who were randomly subjected to one of the following two dietary conditions in a double-blind between-subject approach: (1) The Moja-De ATD challenge (ATD), or (2) TRP-balanced control condition for ATD Moja-De (BAL). Serum concentrations for the assessment of relevant parameters (TNF-α, IL-1β and IL-6) and relevant TRP-related characteristics after the respective challenge procedures were assessed at baseline (T0) and in hourly intervals after administration over a period of 6 h (T1-T6). Results: The ATD condition did not result in significant changes to cytokine concentrations for the entire study sample, or in male and female subgroups. Depletion of CNS 5-HT via dietary TRP depletion appears to have no statistically significant short-term impact on cytokine concentrations in healthy adults. Conclusions: Future research on immunological stressors in combination with challenge techniques will be of value in order to further disentangle the complex interplay between brain 5-HT synthesis and immunological pathways.
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6.
Correlation of different cellular assays to analyze T cell-related cytokine profiles in vitamin D3-supplemented patients with multiple sclerosis.
Rolf, L, Smolders, J, van den Ouweland, J, Hupperts, R, Damoiseaux, J
Molecular immunology. 2019;:198-204
Abstract
Different laboratory approaches have been exploited to analyze an effect of vitamin D3 supplements on T cell cytokine profiles in multiple sclerosis, with poorly reproducible results. We assessed the correlation between intra-cellular flowcytometry analysis of CD4 T cell-enriched CD3+CD8- lymphocytes after PMA/ionomycin stimulation directly ex-vivo or after 72 h pre-stimulation with anti-CD3, and cytokine levels excreted in culture supernatants. Pre-stimulation with anti-CD3 resulted in higher proportions of cells positive for IFN-γ, IL-17 A, IL-4, IL-10 and GM-CSF (all P < 0.001), but not TNF-α. Positive correlation between approaches was highly variable, but most eminent for IFN- γ and IL-4 (R = 0.608-0.612 and R = 0.677-0.777, resp., all P < 0.001). No effect of 16-weeks vitamin D3 supplements on any outcome was found except for a decreased TNF-α concentration in culture supernatants. Choice of immune-assay is, apparently, a relevant confounder for the reproducibility of individual studies.
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7.
Effect of interscalene nerve block on the inflammatory response in shoulder surgery: a randomized trial.
Mejía-Terrazas, GE, Ruíz-Suárez, M, Vadillo-Ortega, F, Franco Y Bourland, RE, López-Muñoz, E
Journal of shoulder and elbow surgery. 2019;(9):e291-e303
Abstract
BACKGROUND Comparing techniques of general anesthesia and regional anesthesia in arthroscopic shoulder surgery, some studies have shown differences in the intensity of immediate postoperative pain and neuroendocrine response, but the inflammatory response when using balanced general anesthesia (BGA) vs. an ultrasound-guided (USG) single-dose interscalene block (SDIB) has not been compared. MATERIALS AND METHODS In a single-center, prospective, randomized clinical trial, the inflammatory response of 2 groups of 10 patients scheduled to undergo arthroscopic shoulder surgery was evaluated through measurement of a panel of cytokines that act on cells of the adaptive immune response to promote or inhibit inflammation, chemokines involved in chemotaxis, the erythrocyte sedimentation rate (ESR), the high-sensitivity C-reactive protein (CRP) level, and the white blood cell (WBC) count in 3 blood samples (before anesthesia, immediately postoperatively, and 24 hours postoperatively) with 2 types of anesthesia (BGA vs. USG SDIB). Postoperative pain intensity (immediately, at 12 hours, and at 24 hours) was also assessed. RESULTS The ESR and CRP level increased significantly at 24 hours after surgery; however, the increase in ESR (P < .0001) and CRP level (P < .0001) was lower in the USG SDIB group. Significant increases in the levels of soluble interleukin 2 receptor α (P = .022) and interleukin 12p40 (P = .016) occurred in the immediate postoperative period in the USG SDIB group. Immediate postoperative pain showed a significant increase (P < .001) in the BGA group. CONCLUSIONS In arthroscopic shoulder surgery, the use of a USG SDIB compared with the use of BGA is possibly associated with improved pain control in the immediate postoperative period and lower immunosuppression, even at 24 hours after surgery.
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8.
[Saliva diagnostic in the research about human immune adaptation to study stress and to differrent water drinking behavior.].
Melnik, KN, Baisheva, GM, Gilmiyarova, FN, Alpatova, TA
Klinicheskaia laboratornaia diagnostika. 2018;(6):353-357
Abstract
85 healthy young people were participates of a randomized placebo controlled cross-over fashion. This study tested associations between different water drinking behavior, the condition of oral immune protection and stress factors over 3 months. We examined saliva IL-1, IL-4, IL-6, TNF-α, γ-IFN, α-amylase and compared them with stress-associated psychophysiological data. As a result of our study we made a saliva pretreatment plan for cytokines and amylase assays, also we tried to understand the strategy of mechanism associations between different water drinking behavior, the condition of oral immune protection and stress factors.
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9.
Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome.
Hustoft, TN, Hausken, T, Ystad, SO, Valeur, J, Brokstad, K, Hatlebakk, JG, Lied, GA
Neurogastroenterology and motility. 2017;(4)
Abstract
BACKGROUND A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is increasingly recommended for patients with irritable bowel syndrome (IBS). We aimed to investigate the effects of a blinded low-FODMAP vs high-fructo-oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short-chain fatty acids (SCFAs). METHODS Twenty patients with diarrhea-predominant or mixed IBS were instructed to follow a low-FODMAP diet (LFD) throughout a 9-week study period. After 3 weeks, they were randomized and double-blindly assigned to receive a supplement of either FOS (FODMAP) or maltodextrin (placebo) for the next 10 days, followed by a 3-week washout period before crossover. Irritable bowel syndrome severity scoring system (IBS-SSS) was used to evaluate symptoms. Cytokines (interleukin [IL]-6, IL-8, and tumor necrosis factor alpha) were analyzed in blood samples, and gut microbiota composition (16S rRNA) and SCFAs were analyzed in fecal samples. KEY RESULTS Irritable bowel syndrome symptoms consistently improved after 3 weeks of LFD, and significantly more participants reported symptom relief in response to placebo (80%) than FOS (30%). Serum levels of proinflammatory IL-6 and IL-8, as well as levels of fecal bacteria (Actinobacteria, Bifidobacterium, and Faecalibacterium prausnitzii), total SCFAs, and n-butyric acid, decreased significantly on the LFD as compared to baseline. Ten days of FOS supplementation increased the level of these bacteria, whereas levels of cytokines and SCFAs remained unchanged. CONCLUSIONS AND INFERENCES Our findings support the efficacy of a LFD in alleviating IBS symptoms, and show changes in inflammatory cytokines, microbiota profile, and SCFAs, which may have consequences for gut health.
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10.
Long-term sex-differential effects of neonatal vitamin A supplementation on in vitro cytokine responses.
Jensen, KJ, Søndergaard, MJ, Andersen, A, Martins, C, Erikstrup, C, Aaby, P, Flanagan, KL, Benn, CS
The British journal of nutrition. 2017;(11):942-948
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Abstract
High-dose vitamin A supplementation (VAS) may affect mortality to infectious diseases in a sex-differential manner. Here, we analysed the long-term immunological effects of neonatal vitamin A supplementation (NVAS) in 247 children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg and 7·5mg retinol equivalents, respectively) or placebo at birth. At 4-6 months of age, we assessed bacille Calmette-Guérin (BCG) scarification, and we analysed in vitro responses of TNF-α, IL-5, IL-10, IL-13 and IFN-γ in whole blood stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (P for interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were increased in females but decreased in males. In addition, IL-17 responses tended to be increased in NVAS v. placebo recipients in males but not in females, significantly so for the PHA stimulation. The study corroborates sex-differential effects of VAS on the immune system, emphasising the importance of analysing VAS effects by sex.