scholarly journals Damage-Associated Molecular Patterns and Th-Cell-Related Cytokines Released after Progressive Effort

2020 ◽  
Vol 9 (3) ◽  
pp. 876 ◽  
Author(s):  
Dorota Kostrzewa-Nowak ◽  
Andrzej Ciechanowicz ◽  
Jeremy S.C. Clark ◽  
Robert Nowak

Inflammation-induced processes commence with the activation of signalling pathways at the cellular level, which mobilize inflammatory cells and stimulate the secretion of chemokines, cytokines, and damage-associated molecular pattern molecules (DAMPs). Physical effort stimulates inflammation, contributing to muscle repair and regeneration. We have examined the impact of different protocols of progressive-effort tests on T-cell DAMP levels, extracellular cleavage products (fibronectin and hyaluronan), and Th-cell-related cytokine levels among soccer players. Thirty male soccer players with a median age of 17 (16–22) years performed different defined protocols for progressive exercise until exhaustion: (1) YO-YO intermittent recovery test level 1 (YYRL1, n = 10); (2) maximal multistage 20 m shuttle run (Beep, n = 10); and mechanical treadmill (MT, n = 10); and (3) shuttle-run test (n = 10). Blood samples were taken three times as follows: at baseline, post effort, and in recovery. Significantly higher post-effort concentrations of IL-4, IL-6, IL-10, and IFN-γ were observed in the Beep group, IL-4 in the YYRL1 group, and IL-6 and IFN-γ in the MT group as compared with the baseline values. Recovery values were significantly higher for concentrations of IL-4, IL-10, and IFN-γ in the YYRL1 group, only for IFN-γ in the Beep group, and for IL-6, IL-10, and INF-γ in the MT group as compared with the baseline values. Post-effort concentrations of DEFβ2, Hsp27, Fn, and UA in the Beep group and Hsp27 and HA in the YYRL1 group were significantly higher as compared with the baseline values. It seems the performed efficiency test protocols caused a short-term imbalance in Th1/Th2 cytokine levels without giving common molecular patterns. The rapidity of these changes was apparently related to specific physical movements and the type of running surface.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16149-e16149
Author(s):  
J. Yuan ◽  
F. Orlandi ◽  
M. Jefferson ◽  
H. Li ◽  
H. Gallardo ◽  
...  

e16149 Background: Ipilimumab (Ipi) is a human IgG1 monoclonal antibody that blocks the inhibitory action of the checkpoint molecule CTLA-4. Recent data [Proc Amer Soc Clin Onc, Abstr#5004, 2008] from castrate metastatic PC pts suggested that Ipi was active but was associated with grade 3 autoimmune adverse events (AEs), such as colitis, hepatitis, hypophysitis or rash, which required high dose steroids. We studied pts who were treated on a clinical trial with Ipi 10 mg/kg alone or with radiation to a single site in bone to determine whether there was any correlation between serum cytokine levels and autoimmune AEs. Methods: Thirteen pts were treated, of whom 10 had sufficient specimens for analysis. Of the 10 pts, 8 had ≥1 AE during treatment. Pts were stratified by ascertainment of clinical benefit (CB) vs. no clinical benefit (NCB) based on time-to-PSA-baseline relapse (TTBR) and also by toxicity (tox) using standard NCI tox criteria. TTBR was defined as time from study entry until the time when a PSA measurement reached or exceeded the baseline value. Pts with a TTBR greater than the median value were judged to have CB; those with a TTBR less than the median value had NCB. Pts with grade (gd) 0/1/2 tox were termed “low tox” while those with gd 3/4 tox were “high tox”. Sera at serial time points were analyzed for interferon-gamma (IFN-γ), tumor necrosis factor α and interleukins (IL)-1b, 2, 4, 8, 10, 12, 13 with the Meso Scale Discovery Multiplex Assay (MSD, Gaithersburg, MD). Results: IFN-γ was the predominant cytokine produced in 4 of 5 pts with CB and AEs; it increased at week 4 or 7 after two doses of Ipi, then declined. Four of 5 pts with NCB had minimal IFN-γ production. There was no difference in IL-10 production between those with CB vs. NCB or high vs. low tox. However, there was a suggestion that the IFN-γ /IL-10 ratio may be increased in pts who had high tox and/or CB vs. pts with low tox and NCB. This awaits confirmation. Conclusions: While this experience with Ipi in PC is small, there may be differences between pts with CB vs. NCB and pts with low vs. high tox. Investigation of the immunophenotype of pts who remain in follow- up and continue to be enrolled is ongoing as well as the impact of prior chemotherapy on development of toxicities. [Table: see text]


2021 ◽  
Author(s):  
Maria Luisa Barcena ◽  
Misael Estepa ◽  
Louis Marx ◽  
Anne Breiter ◽  
Natalie Haritonow ◽  
...  

Abstract Background: Studies have shown that lipoproteins, including LDL, VLDL, and ApoE2 have an impact on macrophage polarization, important to atherosclerosis progression. PCSK9 is a key mediator regulating the expression of lipoprotein receptors. The present study investigates the effect of the VLDL/VLDL-R axis on mononuclear cell polarization, as well as the role of PCSK9 and PCSK9 inhibitors (PCSK9i) within this network.Methods: Human monocytic THP-1 cells and human monocyte-derived macrophages isolated from PBMC were treated with LPS/IFN-γ to induce a pro-inflammatory phenotype or with IL-4 /IL-13 to induce an anti-inflammatory phenotype. Cells were then subjected to further treatments including VLDL, LDL, PCSK9, PCSK9i, anti-LDL-R; PMA and TSP-1.Results: LPS/IFN-γ treatment promoted a pro-inflammatory state with an increased expression of pro-inflammatory mediators e.g., TNF-α, CD80, and IL-1β. VLDL co-treatment induced a switch of this pro-inflammatory phenotype to an anti-inflammatory phenotype. In pro-inflammatory cells, VLDL significantly decreased the expression of the M1-markers e.g., TNF-α, CD80, and IL-1β. These effects were eliminated by PCSK9 and restored by co-incubation with a PCSK9i. Migration assays demonstrated that pro-inflammatory cells displayed a significantly higher invasive capacity compared to untreated cells or anti-inflammatory cells. Moreover, pro-inflammatory cell chemotaxis was significantly decreased by VLDL-mediated acquisition of the anti-inflammatory phenotype. PCSK9 significantly lessened this VLDL-mediated migration inhibition, which was reversed by the PCSK9i.Conclusion: VLDL promotes macrophage differentiation towards the anti-inflammatory phenotype. PCSK9, via its capacity to inhibit VLDL-R expression, reverses the VLDL-mediated anti-inflammatory switch, thereby promoting a pro-inflammatory phenotype. Thus, anti-PCSK9 therapies may exert pro-inflammatory suppression within the vessel wall.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Xu ◽  
Han Wu ◽  
Yuehong Bian ◽  
Linlin Cui ◽  
Yuanyuan Man ◽  
...  

Abstract Background With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. Methods A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. Results Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = − 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). Conclusions Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.


2015 ◽  
Vol 26 (3-4) ◽  
pp. 116-123
Author(s):  
A. P. Korzh ◽  
T. V. Zahovalko

Recently, the number of published works devoted to the processes of synanthropization of fauna, is growing like an avalanche, which indicates the extreme urgency of this theme. In our view, the process of forming devices to coexist with human and the results of his life reflects the general tandency of the modern nature evolution. Urbanization is characteristic for such a specific group of animals like amphibians, the evidence of which are numerous literature data. Many researchers use this group to assess the bioindicative quality of the environment. For this aim a variety of indicators are used: from the cellular level of life of organization up to the species composition of the group in different territories. At the same time, the interpretation of the results is not always comparable for different areas and often have significantly different interpretations by experts. Urban environment, primarily due to the contamination is extremely aggressive to amphibians. As a consequence, the urban populations of amphibians may be a change in the demographic structure, affecting the reproductive ability of the population, the disappearance of the most sensitive species or individuals, resizing animals, the appearance of abnormalities in the development, etc. At the same time play an important amphibians in the ecosystems of cities, and some species in these conditions even feel relatively comfortable. Therefore, it is interesting to understand the mechanisms of self-sustaining populations of amphibians in urban environments. To assess the impact of natural and anthropogenic factors on the development of amphibian populations were used cognitive modeling using the program Vensim PLE. Cognitive map of the model for urban and suburban habitat conditions were the same. The differences concerned the strength of connections between individual factors (migration, fertility, pollution) and their orientation. In general, factors like pollution, parasites, predators had negative impact on the population, reducing its number. The birth rate, food and migration contributed to raising number of individuals. Some of the factors affected on the strength to of each other as well: the majority of the factors affected the structure of the population, had an influence on the fertility. Thanks to it the model reflects the additive effect of complex of factors on the subsequent status of the population. Proposed and analyzed four scenarios differing strength and duration of exposure. In the first scenario, a one-time contamination occurs and not subsequently repeated. The second and third scenario assumes half board contamination, 1 year (2 scenario) and two years (scenario 3). In the fourth scenario, the pollution affected the population of amphibians constantly. In accordance with the results of simulation, much weaker than the natural populations respond to pollution - have them as an intensive population growth and its disappearance at constant pollution is slow. Changes to other parameters of the model showed that this pollution is the decisive factor -only the constant action leads to a lethal outcome for the populations. All other components of the model have a corrective effect on the population dynamics, without changing its underlying trand. In urban areas due to the heavy impact of pollution maintaining the population is only possible thanks to the migration process – the constant replenishment of diminishing micropopulations of natural reserves. This confirms the assumption that the form of existence metapopulations lake frog in the city. In order to maintain the number of amphibians in urban areas at a high level it is necessary to maintain existing migration routes and the creation of new ones. Insular nature of the placement of suitable habitats in urban areas causes the metapopulation structure of the types of urbanists. Therefore, the process of urbanization is much easier for those species whicht are capable of migration in conditions of city. In the initial stages of settling the city micropopulationis formed by selective mortality of the most susceptible individuals to adverse effects. In future, maintaining the categories of individuals is provided mainly due to migration processes metapopulisation form of the species of existence is supported). It should be noted that the changes in the previous levels are always saved in future. In the case of reorganizations of individuals we of morphology can assume the existence of extremely adverse environmental conditions that threaten the extinction of the micropopulations. 


2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis


2020 ◽  
Vol 18 (5) ◽  
pp. 354-361
Author(s):  
Gülay Okay ◽  
Meliha Meric Koc ◽  
Eray Metin Guler ◽  
Ayşegül Yabaci ◽  
Abdürrahim Kocyigit ◽  
...  

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.


2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 255
Author(s):  
Wilmer Cuervo ◽  
Lorraine M. Sordillo ◽  
Angel Abuelo

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.


Author(s):  
Rhys Morris ◽  
Tony Myers ◽  
Stacey Emmonds ◽  
Dave Singleton ◽  
Kevin Till

Abstract Purpose Sled towing has been shown to be an effective method to enhance the physical qualities in youth athletes. The aim of this study was to evaluate the impact of a 6-week sled towing intervention on muscular strength, speed and power in elite youth soccer players of differing maturity status. Method Seventy-three male elite youth soccer players aged 12–18 years (Pre-Peak Height Velocity [PHV] n = 25; Circa-PHV n = 24; Post-PHV n = 24) from one professional soccer academy participated in this study. Sprint assessments (10 m and 30 m), countermovement jump and isometric mid-thigh pull were undertaken before (T1) and after (T2) a 6-week intervention. The training intervention consisted of 6 weeks (2 × per week, 10 sprints over 20 m distance) of resisted sled towing (linear progression 10%–30% of body mass) during the competitive season. Bayesian regression models analysed differences between T1 and T2 within each maturity group. Results There were minimal changes in strength, speed and power (P = 0.35–0.80) for each maturity group across the 6-week intervention. Where there were changes with greater certainty, they are unlikely to represent real effect due to higher regression to the mean (RTM). Conclusion It appears that a 6-week sled towing training programme with loadings of 10%–30% body mass only maintains physical qualities in elite youth soccer players pre-, circa-, and post-PHV. Further research is required to determine the effectiveness of this training method in long-term athletic development programmes.


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