scholarly journals Melatonin as an immunomodulator in children with Down syndrome

2021 ◽  
Author(s):  
Dean Huggard ◽  
Lynne Kelly ◽  
Amy Worrall ◽  
Eleanor Gallagher ◽  
Lida Fallah ◽  
...  
Keyword(s):  
Immune Response ◽  
Down Syndrome ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
List Type ◽  
Tlr4 Expression ◽  
Immunomodulatory Effects ◽  
Children With Down Syndrome ◽  
Anti Inflammatory ◽  
Tlr Signalling

Abstract Background Down syndrome (DS) is a disorder characterised by marked immune dysfunction, increased mortality from sepsis, chronic inflammation, increased oxidative stress, sleep disturbance and possibly abnormal endogenous melatonin levels. Melatonin has a myriad of immune functions, and we hypothesised that this therapeutic agent could modulate the innate immune system in this cohort. Methods We investigated neutrophil and monocyte function (CD11b, TLR4 expression by flow cytometry), genes involved in TLR signalling (MyD88, IRAK4, TRIF), the inflammasome (NLRP3, IL-1β), and circadian rhythm (BMAL, CLOCK, CRY) by qPCR, and inflammatory cytokines (IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ, IL-10, IL-1ra, VEGF, Epo, GM-CSF) by enzyme-linked immunosorbent assay (ELISA) following immunomodulation with LPS endotoxin and melatonin. 47 children with DS and 23 age- and sex-matched controls were recruited. Results We demonstrated that melatonin has several significant effects by reducing CD11b and TLR4 expression, attenuating TLR signalling, genes involved in the inflammasome and has the potential to reduce LPS-induced inflammatory responses. Conclusions Immunomodulatory effects of melatonin were found in both paediatric cohorts with more marked effects in the children with DS. Melatonin mediates immune response through a wide array of mechanisms and this immunomodulator may buffer the inflammatory response by regulating pro and anti-inflammatory signalling. Impact We highlight that melatonin mediates its immune response through a wide array of mechanisms, its effects appear to be dose dependant and children with Down syndrome may be more receptive to treatment with it. Immunomodulatory effects of melatonin were demonstrated with marked effects in the children with Down syndrome with a reduction of MyD88, IL-1ß and NLRP3 expression in whole-blood samples. Melatonin is a proposed anti-inflammatory agent with a well-established safety profile, that has the potential for mitigation of pro- and anti-inflammatory cytokines in paediatric Down syndrome cohorts, though further clinical trials are warranted.

scholarly journals Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Human Muscle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Muscle Stem Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

scholarly journals Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1035
Author(s):  
Maha Sellami ◽  
Shamma Al-muraikhy ◽  
Hend Al-Jaber ◽  
Hadaia Al-Amri ◽  
Layla Al-Mansoori ◽  
...  
Keyword(s):  
Immune Response ◽  
Telomere Length ◽  
Inflammatory Cytokines ◽  
Elite Athletes ◽  
Age Groups ◽  
Moderate Intensity ◽  
Necrosis Factor Alpha ◽  
Blood Samples ◽  
Tnf Α ◽  
Anti Inflammatory

Background: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. Methods: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Results: Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. Conclusion: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

scholarly journals Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

2021 ◽  
Vol 18 (16) ◽  
pp. 8538
Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Control Group ◽  
Study Group ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

scholarly journals Dynamic Evaluation of Compound Ento-PB for the Repair of Mucosal Ulcer in Dogs With Acetic Acid-induced Experimental Colitis 

2020 ◽  
Author(s):  
Jin-hu Chen ◽  
Jian-ting Zhao ◽  
Zheng-yong Yu ◽  
Yi-hao Che ◽  
Yu-jia Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Inflammatory Cytokines ◽  
Mucosal Healing ◽  
Dynamic Monitoring ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Expression Levels ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract Background: Mucosal inflammation and ulcer play important roles in the pathogenesis of ulcerative colitis. As as traditional Chinese medicine compound composed of Periplaneta americana and Taraxacum mongolicum, Ento-PB is always prescribed for the treatment of ulcer and inflammatory diseases. As for the significant role of P. americana in terms of promoting mucosal healing, the compatibility of the anti-inflammatory drug T. mongolicum may enable Ento-PB to simultaneously play anti-inflammatory and promote mucosal healing effects on the treatment of UC. Therefore, this study aimed to evaluate the therapeutic potential and possible mechanism of Ento-PB for UC by establishing an acetic acid-induced colitis model in dogs.Methods: Preliminary identification to the chemical components of compound Ento-PB was carried out through high performance liquid chromatography. A cross-bred dogs model of acetic acid-induced ulcerative colitis was established to evaluate the efficacy of compound Ento-PB. The expression levels of inflammatory cytokines C-reactive protein (CRP), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma were measured by carrying out enzyme-linked immunosorbent assay (ELISA).Results: With the extension of treatment time, Ento-PB could effectively improve clinical symptoms of UC cross-bred dogs. Colonoscopy displayed that mucosal redness, swelling and congestion decreased gradually, and obviously repaired after mucosal injury. The intestinal texture was gradually clear, and the colonoscopy score gradually reduced. Histopathological examination revealed that the structure of colon was restored significantly, the infiltration of inflammatory cells was reduced, and the histological score was remarkably reduced. At the same time, the results of dynamic monitoring of inflammatory cytokines in plasma proved that Ento-PB can gradually down-regulate the activity of CRP, iNOS and COX-2, reduce the expression levels of inflammatory cytokines TNF-α and IL-1β, and gradually restore anti-inflammatory and the expression level of cytokine IL-10.Conclusions: Ento-PB reduces the level of pro-inflammatory cytokines in a dose- and time-dependent manner and inflammation, improves colon tissue lesions and the repair of intestinal mucosa after injury, and effectively increases acetic acid-induced colon inflammation in UC cross-bred dogs.

scholarly journals Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

2020 ◽  
Author(s):  
Bruna Lima Correa ◽  
Nadia El Harane ◽  
Ingrid Gomez ◽  
Hocine Rachid Hocine ◽  
José Vilar ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Nk Cell ◽  
Inflammatory Monocytes ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.

scholarly journals 13 Lipocalin 2 exerts protective activity by alleviating inflammatory responses

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 17-19
Author(s):  
Shuhui Li
Keyword(s):  
Inflammatory Cytokines ◽  
Protective Factor ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipocalin 2 ◽  
Continuous Increase ◽  
Raw264.7 Macrophages ◽  
Arginase 1 ◽  
Anti Inflammatory

Abstract Lipocalin 2 (Lcn2) is an essential component of the innate immune system and exerts significant immunomodulatory effects in vitro. The aim of current study was to investigate the expression profile of Lcn2 during inflammatory process and explore the role of Lcn2 in the anti-inflammatory responses. Western blot, real-time quantitative PCR, immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) were employed. Firstly, we evaluated the temporospatial expression of Lcn2 of mice after inflammatory stimuli by lipopolysaccharides (LPS). In vivo, LPS induced both mRNA and protein levels of Lcn2 significantly (P < 0.01) in liver, jejunum and ileum. Lcn2 exhibited a continuous increase by 8 h and peaked by 24 h post challenges. Secondly, we challenged Lcn2-deficient (Lcn2-/-) mice and wild-type (WT) mice with peripheral LPS and determined effects on inflammation. In contrast to WT mice, Lcn2-/- mice showed distinct inflammatory injury in liver, jejunum, ileum and spleen with significantly elevated pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1b (IL-1b) and decreased anti-inflammatory cytokine interleukin-10 (IL-10). Thirdly, we isolated bone marrow-derived macrophages (BMDM) from Lcn2-/- mice and WT mice to evaluate their functions. After LPS challenge, Lcn2-/- BMDM showed aggravated inflammatory reaction as pro-inflammatory factors tumour necrosis factor-α (TNF-α), IL-6, IL-1b and inducible nitric oxide synthase (iNOS) increased (P < 0.05) while anti-inflammatory cytokines IL-10, transforming growth factor β1 (TGF-β1) and arginase-1(Arg-1) decreased significantly (P < 0.05) compared with WT BMDM. This phenomenon could be relieved when adding recombinant Lcn2 (P < 0.05). The exogenous addition of Lcn2 on mice RAW264.7 macrophages stimulated by LPS also conformed this point. These findings demonstrated that Lcn2 served as a potent protective factor in response to systemic inflammation, and elevated Lcn2 expression during inflammatory conditions was presumed to play an effective role in alleviating inflammatory responses.

scholarly journals Pro- and Anti-Inflammatory Cytokine Balance in Major Depression: Effect of Sertraline Therapy

2007 ◽  
Vol 2007 ◽  
pp. 1-6 ◽  
Author(s):  
Levent Sutcigil ◽  
Cagatay Oktenli ◽  
Ugur Musabak ◽  
Ali Bozkurt ◽  
Adnan Cansever ◽  
...  
Keyword(s):  
Major Depression ◽  
Inflammatory Cytokines ◽  
Antidepressant Treatment ◽  
Depression Effect ◽  
Immunomodulatory Effects ◽  
Cytokine Balance ◽  
Anti Inflammatory ◽  
Time Of Admission ◽  
Anti Inflammatory Cytokine

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-α, TGF-β1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-α) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-β1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-β1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

Anti-inflammatory and immunomodulatory effects of Critonia aromatisans leaves: Downregulation of pro-inflammatory cytokines

2016 ◽  
Vol 190 ◽  
pp. 174-182 ◽  
Author(s):  
Villa-De la Torre Fabiola ◽  
Kinscherf Ralf ◽  
Bonaterra Gabriel ◽  
Arana-Argaez Victor Ermilo ◽  
Méndez-González Martha ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Immunomodulatory Effects ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

scholarly journals Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

2013 ◽  
Vol 81 (11) ◽  
pp. 4001-4012 ◽  
Author(s):  
Mónica González-Pérez ◽  
Leonardo Mariño-Ramírez ◽  
Carlos Alberto Parra-López ◽  
Martha Isabel Murcia ◽  
Brenda Marquina ◽  
...  
Keyword(s):  
Immune Response ◽  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokines ◽  
Mycobacterium Avium ◽  
High Expression ◽  
High Dose ◽  
Content Type ◽  
Subcutaneous Infection ◽  
Tnf Α ◽  
Anti Inflammatory

ABSTRACTThe genusMycobacteriumcomprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies withMycobacterium tuberculosis. The biological differentiation betweenM. tuberculosisand nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not.Mycobacterium aviumcomplex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after theM. tuberculosiscomplex. Here, we evaluated the virulence and immune response ofM. aviumsubsp.aviumandMycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.

Sign in / Sign up

Export Citation Format

Share Document