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Effect of montelukast combined with methylprednisolone for the treatment of mycoplasma pneumonia.
Wu, H, Ding, X, Zhao, D, Liang, Y, Ji, W
The Journal of international medical research. 2019;(6):2555-2561
Abstract
OBJECTIVE To study the effect of the leukotriene receptor agonist montelukast combined with methylprednisolone on inflammatory response and peripheral blood lymphocyte subset content in children with mycoplasma pneumonia. METHODS Seventy-four children were enrolled and randomly divided into a standard treatment group and a montelukast plus methylprednisolone group. Serum levels of inflammatory cytokines and corresponding cytokines of T lymphocyte subsets were measured, and peripheral blood was collected to determine the T cell subset content. RESULTS At 3 days and 7 days after treatment, serum MCP-1, PCT, ICAM-1, CXCL8, CRP, IFN-γ, and IL-17 levels and peripheral blood Th1 and Th17 content were significantly decreased in both groups, while serum IL-4 and TGF-β levels and peripheral blood Treg and Th2 content were significantly increased. However, serum MCP-1, PCT, ICAM-1, CXCL8, CRP, IFN-γ, and IL-17 levels and peripheral blood Th1 and Th17 content were significantly lower while serum IL-4 and TGF-β levels and peripheral blood Treg and Th2 content were significantly higher in the montelukast plus methylprednisolone group compared with the control group. CONCLUSION Montelukast combined with methylprednisolone for the treatment of mycoplasma pneumonia can inhibit inflammatory responses and regulate levels of Th1/Th2 and Th17/Treg cells.
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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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Non-muscle myosin IIA is post-translationally modified by interferon-stimulated gene 15 in breast cancer cells.
Cruz-Ramos, E, Macías-Silva, M, Sandoval-Hernández, A, Tecalco-Cruz, AC
The international journal of biochemistry & cell biology. 2019;:14-26
Abstract
ISG15 (interferon-stimulated gene 15) exists as free ISG15 or conjugated ISG15 modifying its target proteins via ISGylation. Few proteins have been identified and studied as ISGylation targets, and their relevance is not completely clear. Here, we isolated ISG15 from MDA-MB-231 breast cancer cells using immunoprecipitation and identified non-muscle myosin IIA (NMIIA) using mass spectrometry as endogenously associated with ISG15. The identification of NMIIA as an ISG15-interacting protein was important, because levels of NMIIA mRNA were not deregulated in all breast cancers, and because our in silico analysis indicated that NMIIA was the target of different posttranslational modifications and had an interactome associated with cytoskeletal remodeling. Furthermore, our experimental assays of co-immunoprecipitation and immunofluorescence confirmed that ISG15 was covalently associated with NMIIA in the cytoplasm of breast cancer cells and that interferon γ (IFN-γ) increased this association without alterations in the NMIIA levels. Thus, NMIIA ISGylation is regulated by IFN-γ, and this modification may modulate its interactions with proteins that remodel the cytoskeleton, participating in the growth and progression of mammary tumors.
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Aqueous Humor Mediator and Cytokine Aberrations in Diabetic Retinopathy and Diabetic Macular Edema: A Systematic Review and Meta-Analysis.
Wu, J, Zhong, Y, Yue, S, Yang, K, Zhang, G, Chen, L, Liu, L
Disease markers. 2019;:6928524
Abstract
PURPOSE To evaluate the relationship between the aqueous humor levels of VEGF, TNF-α, IL-10, IL-6, IL-12, MCP-1, and IP-10 with DR/DME. METHODS PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched up to October 2018. Systematic review and meta-analysis were conducted. RESULTS 18 studies comprising 362 cases with DR (100 with DME) and 620 controls without DR were included in this meta-analysis. There was a significant association between VEGF levels in the aqueous humor and DR (standardized mean difference (SMD) 1.94 (95% CI 1.05-2.83)) and DME (1.07 (0.71, 1.42)). Furthermore, a significant correlation was observed between levels of IL-6 and DR (3.53 (0.37, 6.69)), and similarly correlation with DME (1.26 (0.30, 2.21)). The relationship between MCP-1 and DR and DME was significant, in which the SMD was (0.49 (0.09, 0.89)) and (1.49 (0.78, 2.20)), respectively. However, IL-12, IP-10, and TNF-α had no correlation with DR and DME, whereas there was a significant relationship between IL-8 and DME (1.68 (0.97, 2.40)). CONCLUSION Elevated levels of VEGF, IL-6, and MCP-1 in the aqueous humor were associated with the risk for the presence of DR, and levels of VEGF, IL-6, IL-8, and MCP-1 were associated with the risk of DME. Furthermore, these biomarkers may be used as potential predictors or therapeutic targets for DR/DME.
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Cytokine, glycemic, and insulinemic responses to an acute bout of games-based activity in adolescents.
Dring, KJ, Cooper, SB, Morris, JG, Sunderland, C, Foulds, GA, Pockley, AG, Nevill, ME
Scandinavian journal of medicine & science in sports. 2019;(4):597-605
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Abstract
An acute bout of endurance exercise in adults stimulates a same-day anti-inflammatory response which may affect low-grade chronic inflammation and insulin resistance and benefit cardio-metabolic health. The anti-inflammatory responses to intermittent games-based exercise and to exercise in young people beyond 2 hours post-exercise are unknown. Thus, the purpose of the present study is to examine the anti-inflammatory, glycemic and insulinemic response to games-based activity in adolescents. Following ethical approval and familiarization, 39 adolescents (12.3 ± 0.7 years) completed an exercise (E) and rested (R) trial in a counterbalanced, randomized crossover design. Following a standardized breakfast, participants completed 1-hour games-based activity. Capillary blood samples were taken at baseline, immediately and 1 hour post-exercise, and 30, 60 and 120 minutes following a standardized lunch. A final blood sample was taken the next morning. Data were analyzed using repeated measures ANOVA. IL-6 concentration was higher on day one of the exercise trial (E:3.4 ± 0.4, R:2.7 ± 0.4 pg/mL; P = 0.006), as was the anti-inflammatory IL-6:TNF-α ratio (E:5.53 ± 0.93, R:3.75 ± 0.45; P = 0.027). Levels of the anti-inflammatory cytokine IL-10 increased on day two of the exercise trial (E:2.11 ± 0.23, R:1.66 ± 0.16 pg/mL; P = 0.032). Insulin sensitivity was enhanced on the exercise trial with a reduction in iAUC following the standardized lunch (E:2310 ± 834, R:3122 ± 1443 mU/L × 120 minutes; P < 0.001). Games-based activity stimulated an anti-inflammatory response up to 24 hours post-exercise and improved insulin sensitivity in response to a standardized meal in healthy adolescents. These novel findings suggest that games-based activity is an ecologically valid mode of exercise to elicit beneficial effects on cardio-metabolic risk factors in young people.
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The incretin system in healthy humans: The role of GIP and GLP-1.
Holst, JJ
Metabolism: clinical and experimental. 2019;:46-55
Abstract
The incretin effect, the amplification of insulin secretion occurring when glucose is taken in orally as compared to infused intravenously, is one of the factors that help the body to tolerate carbohydrate/glucose ingestion. These include 1) amount and type of carbohydrates; 2) gastric emptying rate; 3) digestion and absorption of the carbohydrates; 4) secretion and effect of the incretin hormones; 5) disposition of absorbed nutrients/glucose. The incretin effect can also be viewed as the fraction of the ingested glucose load handled via gastrointestinal mechanisms (including the incretin effect); it is calculated by comparison of the amount of glucose required to copy, by intravenous infusion, the oral load. Typically, for 75 g of oral glucose, about 25 g are required. This means that the GastroIntestinal Glucose Disposal (GIGD) is 66%. Both the GIGD and the incretin effect depend on the amount of glucose ingested: for higher doses the GIGD may amount to 80%, which shows that this effect is a major contributor to glucose tolerance. The main mechanism behind it is stimulation of insulin secretion by a proportional secretion of the insulinotropic hormones GIP and GLP-1. Recently it has become possible to estimate their contributions in healthy humans using specific and potent receptor antagonists. Both hormones act to improve glucose tolerance (i.e. the antagonists impair tolerance) and their effects are additive. GIP seems to be quantitatively the most important, particularly regarding insulin secretion, whereas the action of GLP-1 is mainly displayed via inhibition of glucagon secretion.
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In vitro cytokine synthesis in unstimulated and mitogen-stimulated peripheral blood mononuclear cells from individuals with schizophrenia.
Kozłowska, E, Żelechowska, P, Wysokiński, A, Rasmus, P, Łucka, A, Brzezińska-Błaszczyk, E
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2019;(7):1053-1060
Abstract
Increasing evidence has shown that the immune system is involved in the schizophrenia development, with alterations in immune cell reactivity being one possible factor contributing to its pathogenesis. The purpose of the study was to evaluate in vitro the capability of peripheral blood mononuclear cells (PBMCs) obtained from subjects with schizophrenia and controls to engage in spontaneous and phytohemagglutinin (PHA)-stimulated cytokine production. The concentrations of various cytokines (interleukin (IL)-1β, IL-17A, tumor necrosis factor (TNF), interferon (IFN)-γ and IL-10) in supernatants from cultured PBMCs were measured using the cytometric bead array. No significant differences in the spontaneous production of IL-1β, IL-17A, IFN-γ and IL-10 by PBMCs were detected between individuals with schizophrenia and controls. TNF synthesis by PBMCs was found to be lower among those with schizophrenia. In all subjects and controls, greater cytokine generation was associated with PBMCs treated with PHA compared with those that were not. The PBMCs from people with schizophrenia displayed considerably higher sensitivity to mitogen stimulation, as the production of IL-17A, TNF and IFN-γ was at least threefold of that observed in healthy subjects, which may be driven by antipsychotics taken by patients with schizophrenia. Correlation was observed between spontaneous production of IFN-γ and Positive and Negative Syndrome Scale G subscore (which measures the general symptoms of schizophrenia) and between PHA-stimulated synthesis of IL-17A and G subscore. Our data confirm that the immune system dysregulation may underlie schizophrenia pathophysiology. There is a potential possibility that immunological tests could be used as a diagnostic, therapeutic and side-effects biomarker for schizophrenia, but further studies are needed.
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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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Cold-water immersion blunts and delays increases in circulating testosterone and cytokines post-resistance exercise.
Earp, JE, Hatfield, DL, Sherman, A, Lee, EC, Kraemer, WJ
European journal of applied physiology. 2019;(8):1901-1907
Abstract
INTRODUCTION Cold-water immersion (CWI) is often used to promote recovery by reducing exercise-induced muscle damage, soreness, and inflammation. However, recent reports have cautioned that CWI may attenuate the adaptive response to resistance training. PURPOSE To determine the effect of post resistance-exercise CWI on circulating free testosterone (T) and cytokine (IL-6 and TNF-α) response. METHODS Using a randomized and counterbalanced repeated-measures design, 11 resistance-trained men completed two workouts (6 sets of 10 repetitions of back squats at 80% of maximum load) a week apart after which they took part in either 15 min of CWI (15 °C) or passive recovery. T, IL-6, and TNFα were measured in blood samples taken before (PRE) and 5 (5POST), 15 (15POST), 30 (30POST), and 60 (60POST) min post-exercise and compared between treatments and over time. RESULTS For T, a significant interaction effect of condition over time (p = 0.030) as well as greater relative concentrations of T in CON (Δ9.2%) than CWI (Δ-0.5%, p = 0.049) at 30POST were observed. In addition, at 60POST, T dropped below PRE values in CWI (Δ-10.4%, p = 0.028) but not in CON (Δ-1.6%, p = 0.850). A suppressed cytokine response was observed after CWI in IL-6 at 30POST (CWI: Δ4.9%, CON: Δ47.5%, p = 0.041) and TNFα at 15POST (CWI: Δ5.3%, CON: Δ17.0%, p = 0.022). CONCLUSIONS CWI blunted the T and cytokine response after a bout of resistance exercise. These results indicate that CWI results in an altered anabolic response and may help to explain the previous observation of attenuated hypertrophy when CWI is used after resistance exercise.
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The effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor and inflammatory cytokines among women with implantation failure.
Hashemi, Z, Sharifi, N, Khani, B, Aghadavod, E, Asemi, Z
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(1):95-102
Abstract
OBJECTIVE Data on the effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor (VEGF) and inflammatory cytokines among women with implantation failure are limited. This research was performed to determine the effects of vitamin E supplementation on endometrial thickness, and gene expression of VEGF and inflammatory cytokines among women with implantation failure. METHODS A randomized clinical trial was done among 40 women with implantation failure aged 18-37 years old. Participants were randomly divided into two groups: group A (n = 20) received 400-IU vitamin E supplements and group B (n = 20) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week treatment to determine biomarkers of oxidative stress, and gene expression of VEGF and inflammatory cytokines. RESULTS After the 12-week intervention, compared with the placebo, women with implantation failure who consumed vitamin E supplements had significantly increased serum vitamin E levels (+18.6 ± 15.0 versus -1.5 ± 1.0 nmol/mL, p < .001) and endometrial thickness (+1.1 ± 0.9 versus -0.5 ± 0.3 mm, p = .01), and significantly decreased plasma malondialdehyde (MDA) concentrations (-0.4 ± 0.3 versus +0.4 ± 0.3 µmol/L, p < .004). In addition, results of RT-PCR demonstrated that compared with the placebo, vitamin E intake downregulated gene expression of low-density lipoprotein receptor (LDLR) (p = .008), interleukin-1 (IL-1) (p = .02), and tumor necrosis factor alpha (TNF-α) (p = .007) in peripheral blood mononuclear cells of women with implantation failure. CONCLUSIONS Overall, vitamin E supplementation for 12 weeks among women with implantation failure had beneficial effects on endometrial thickness, MDA values, and gene expression of LDLR, IL-1, and TNF-α.