scholarly journals Dual Anti-Malarial and GSK3β-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria

2021 ◽  
Vol 14 (3) ◽  
pp. 248
Author(s):  
Amatul Hamizah Ali ◽  
Suhaini Sudi ◽  
Ng Shi-Jing ◽  
Wan Rozianoor Mohd Hassan ◽  
Rusliza Basir ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Cytokine Production ◽  
Glycogen Synthase ◽  
Serum Levels ◽  
Murine Models ◽  
Malarial Infection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Severity Of The Disease ◽  
Inflammatory Signalling

Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3β (GSK3β), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3β-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3β (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3β (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3β-mediated cytokine-modulating effects.

scholarly journals Cytokine Production by Peripheral Blood CD4+and CD8+T Cells in Atopic Childhood Asthma

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Edyta Machura ◽  
Bogdan Mazur ◽  
Malgorzata Rusek-Zychma ◽  
Malgorzata Barć-Czarnecka
Keyword(s):  
T Cells ◽  
Childhood Asthma ◽  
Cytokine Production ◽  
Atopic Asthma ◽  
Asthmatic Children ◽  
Tnf Α ◽  
Duration Of Disease ◽  
Ifn Γ ◽  
Severity Of The Disease ◽  
Relationship Of

There are conflicting studies on T cell cytokine production in childhood asthma. In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN-γ, and TNF-α in CD4+and CD8+T cells in children with atopic asthma were measured by flow cytometry.Results. A significant increase in the percentage of CD4+and CD8+T cells producing IL-4 and IL-13 and decrease in the percentage of CD4+producing IFN-γ in asthmatic children was found. The percentage of CD4+/IL-13+was significantly higher in severe asthma than in children with intermittent disease symptoms. Severity of asthma was associated with increased both serum IgE and frequencies of CD4+/IL-13+T cells, as well as duration of disease. Moreover, a decrease in FEV1, FEV1/FVC was observed in relation to the severity of asthma. Changes in cytokine profile in CD8+subpopulation didn't depend on the severity of the disease.Conclusions. Increased production of IL-4 and IL-13 in both CD4+and CD8+T cells accompanied by decreased IFN-γ expression in CD4+T cells may be evidence that both lymphocyte subpopulations are implicated in the pathogenesis of asthma. Relationship of CD4+/IL-13+T cells with disease activity suggests that this lymphocyte subset may have a prominent role in childhood asthma.

scholarly journals Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

2014 ◽  
Vol 66 (4) ◽  
pp. 1067-1072
Author(s):  
M.A.R. Feliciano ◽  
A.S.L. Silva ◽  
R.M. Crivelaro ◽  
M.E.F. Oliveira ◽  
L.N. Coutinho ◽  
...  
Keyword(s):  
Immune Response ◽  
Natural Killer ◽  
Serum Levels ◽  
Blood Samples ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pathological Pregnancy ◽  
English Bulldog

The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer) in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA) validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05). However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

scholarly journals Distinct PKC-mediated posttranscriptional events set cytokine production kinetics in CD8+ T cells

2017 ◽  
Vol 114 (36) ◽  
pp. 9677-9682 ◽  
Author(s):  
Fiamma Salerno ◽  
Nahuel A. Paolini ◽  
Regina Stark ◽  
Marieke von Lindern ◽  
Monika C. Wolkers
Keyword(s):  
T Cells ◽  
Mrna Stability ◽  
Cytokine Production ◽  
De Novo ◽  
Translation Efficiency ◽  
Mrna Stabilization ◽  
Relative Contribution ◽  
Production Kinetics ◽  
Tnf Α ◽  
Ifn Γ

Effective T cell responses against invading pathogens require the concerted production of three key cytokines: TNF-α, IFN-γ, and IL-2. The cytokines functionally synergize, but their production kinetics widely differ. How the differential timing of expression is regulated remains, however, poorly understood. We compared the relative contribution of transcription, mRNA stability, and translation efficiency on cytokine production in murine effector and memory CD8+ T cells. We show that the immediate and ample production of TNF-α is primarily mediated by translation of preformed mRNA through protein kinase C (PKC)-induced recruitment of mRNA to polyribosomes. Also, the initial production of IFN-γ uses translation of preformed mRNA. However, the magnitude and subsequent expression of IFN-γ, and of IL-2, depends on calcium-induced de novo transcription and PKC-dependent mRNA stabilization. In conclusion, PKC signaling modulates translation efficiency and mRNA stability in a transcript-specific manner. These cytokine-specific regulatory mechanisms guarantee that T cells produce ample amounts of cytokines shortly upon activation and for a limited time.

scholarly journals The Effectiveness of Rapamycin Combined with Eltrombopag in Murine Models of Immune-Mediated Bone Marrow Failure

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Rong Fu ◽  
Shaoxue Ding ◽  
Xiaowei Liang ◽  
Tian Zhang ◽  
Zonghong Shao
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Standard Dose ◽  
Bone Marrow Failure ◽  
Statistical Significance ◽  
Murine Models ◽  
Immune Mediated ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Recent research has found that Rapamycin (Rapa) was an effective therapy in mouse models of immune-mediated bone marrow failure. However, it has not achieved satisfactory effect in clinical application. At present, many studies have confirmed that Eltrombopag (ELT) combined with IST can improve the curative effect of AA patients. Then whether Rapa combined with Elt in the treatment of AA will be better than single drug application. In this study, we tested efficacy of Rapa combined with Elt as a new treatment in mouse models of immune-mediated bone marrow failure. Compared with AA group, the whole blood cell count of Rapa+Elt group increased significantly (Figure 1A) (P<0.05). Survival of mice of Rapa+Elt group was significantly higher than that in the Rapa group (p <0.01)(Figure 1B).There was no obvious difference in the numbers of NK cells and their subsets were noted in Rapa group,CsA group and Rapa+Elt group.The expression of NKG2D on peripheral functional NK cells was up-regulated in CsA group, Rapa group and Rapa+Elt group compared with AA group (P<0.05). But there was no significant difference between effect of Rapa and CsA on the function of NK cells (Figure 1C).When Rapa combined with Elt, the expression of CD80 and CD86 are down-regulated more compared to Rapa group, but there is no statistical significance. Although these results suggested that Rapa+Elt had no statistical significance effect on numbers of mDC and expression of its functional molecule CD80 and CD86, the combined therapy still indicated that there is a potential synergy with immunosuppressant on AA mice to improve its outcome (Figure 1D).The results showed that CD4+/CD8+ ratio in CsA group, Rapa group, Rapa + Elt group had an obvious elevation than AA group (all P<0.05). But there were no significant difference among the three groups on the CD4+/CD8+ ratio (Figure 1E,1F). As for INF-gamma, Rapa can reduce the secretion of IFN-γ from CD8+T cells with efficacy similar to that of the standard dose of CsA, and had a better outcome when combined with Elt in bone marrow failure mice (Figure 1E,1G).CsA group, Elt group, Rapa group, Rapa + Elt group showed notable increased ratio of Tregs compared with AA group, among which there were only Rapa group, Rapa + Elt group showed statistical significance(P<0.05). for IL-10/Tregs ratio, Rapa group and Rapa +Elt group were superior to than CsA group(P<0.05) (Figure 1H,1I).Rapa+Elt group and Rapa showed more lower level of IFN-γ compared with CsA group, and there was significant difference in Rapa+Elt group(P<0.05). As for IL-10, IL-12p70, IL-2, IL-6, KC/GRO and TNF-α, the Rapa+Elt group showed more significant effect than Rapa or Elt alone(Figure1J). Thus, Rapa+Elt significantly down-regulated cytokines related to Th1 immune responses, such as IFN-γ, and upregulated cytokines related to Th2 immune responses, such as IL-10. To some extent, Rapa combined with Elt has a synergistic effect with CsA and Rapa alone in AA treatment. Conclusions In this study, Although Rapa combined with Elt had no significant improvement effect on the number and function of NK cells and their subsets, mDCs, and CD4+/CD8+ ratio in AA mice compared with Rapa alone, the Rapa+Elt can increase the secretion of IL-10 of Tregs and the number of Tregs, but has no significant effect on the number of Treg cells compared to with Rapa alone. Compared with AA group, the level of plasma IFN-γ, IL-2 and TNF-α decreased significantly (P<0.05), but IL-10, IL-4, IL-5 and IL-1β increased significantly in Rapa group(P<0.05). As for IL-10, IL-12p70, IL-2, IL-6, KC/GRO and TNF-α, the Rapa+Elt group showed more significant effect than Rapa alone. intervention treatment with Rapa in combination Elt in the AA mouse model more obviously ameliorated pancytopenia, improved bone marrow cellularity, and extended animal survival in a manner comparable to the standard dose of CsA and Rapa alone. Combination therapy support potential clinical utility in aplastic anemia treatment, which may further improve the efficacy of AA patients. Keywords: Rapamycin, Eltrombopag, murine models, bone marrow failure Figure 1 Disclosures No relevant conflicts of interest to declare.

Clinical significance of cytokine markers in children with different courses of community-acquired pneumonia

2020 ◽  
Vol 15 (5) ◽  
pp. 18-23
Author(s):  
G.P. Evseeva ◽  
◽  
G.N. Kholodok ◽  
S.V. Pichugina ◽  
S.V. Suprun ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Interleukin 1 ◽  
Interferon Γ ◽  
Peripheral Blood Lymphocytes ◽  
Community Acquired Pneumonia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Ifn Γ

Principles of the diagnosis and treatment of community-acquired pneumonia (CAP) in children were developed and clearly formulated long ago. Nevertheless, clinicians often encounter the problem of pulmonary and pleural complications of CAP, which is challenging in terms of the choice of initial therapy, since the first symptoms of uncomplicated and complicated pneumonia are often similar. Therefore, the search for early markers of complicated CAP in children is highly important. Objective. To assess prognostic values of spontaneous and mitogen-induced cytokine production in children with CAP. Patients and methods. We have performed comprehensive examination of 108 children with CAP. Eighty-four of them had uncomplicated CAP, whereas 24 children had CAP complicated by pleurisy. We measured spontaneous and induced production of the following cytokines upon patient admission to hospital: interleukin-1 (IL-1), interleukin-17 (IL-17), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). To measure induced cytokine production, we stimulated peripheral blood lymphocytes by S. рneumonае (serotype 7, 11; strains 7C and 11AD). The level of cytokines was evaluated using the enzyme-linked immunosorbent assay (Vektor-BEST, Novosibirsk, Russia). Results. We found that in children with uncomplicated CAP, induction of immunocompetent blood cells (IBCs) led to increased secretion of first-generation cytokines, including IL-1, TNF-α, and IFN-γ, whereas IBCs of patients with complicated CAP primarily produced second-generation cytokines, including VEGF, МРС-1, and IL-17. Conclusion. The observed differences in spontaneous and mitogen-induced cytokine production between children with and without CAP complications suggest that these parameters can be considered as promising prognostic markers for complicated CAP in children. The proposed method can be used in pediatric practice to predict the development of complications in children with CAP. Key words: children, community-acquired pneumonia, cytokines

scholarly journals Invariant Vα14 Chain NKT Cells Promote Plasmodium berghei Circumsporozoite Protein-Specific Gamma Interferon- and Tumor Necrosis Factor Alpha-Producing CD8+ T Cells in the Liver after Poxvirus Vaccination of Mice

2005 ◽  
Vol 73 (2) ◽  
pp. 849-858 ◽  
Author(s):  
Simone Korten ◽  
Richard J. Anderson ◽  
Carolyn M. Hannan ◽  
Eric G. Sheu ◽  
Robert Sinden ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Plasmodium Berghei ◽  
Tumor Necrosis ◽  
Nkt Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-γ)-producing CD8+ T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Vα14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Vα14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Vα14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing pre-erythrocytic stage antigen-specific CD8+ T cells. Greater numbers of hepatic Vα14iNKT cells secreted interleukin-4 than IFN-γ. Vaccinated Vα14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-γ+ and TNF-α+ CD8+ T cells and better protection rates later after challenge with Plasmodium berghei sporozoites. Therefore, vaccine-activated hepatic Vα14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-γ+/TNF-α+ CD8+ T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.

scholarly journals Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis

2013 ◽  
Vol 39 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Beatriz Lima Alezio Muller ◽  
Daniela Maria de Paula Ramalho ◽  
Paula Fernanda Gonçalves dos Santos ◽  
Eliene Denites Duarte Mesquita ◽  
Afranio Lineu Kritski ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Pulmonary Tuberculosis ◽  
Gene Polymorphisms ◽  
Serum Levels ◽  
Acute Inflammatory Response ◽  
Reactive Protein ◽  
Antituberculosis Treatment ◽  
Tnf Α ◽  
Referral Hospitals ◽  
Ifn Γ

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.

Virulence comparison of human and poultry Campylobacter jejuni isolates in a mouse model

2017 ◽  
Vol 5 (10) ◽  
Author(s):  
Darinka Vučković ◽  
Maja Šikić Pogačar ◽  
Peter Raspor ◽  
Maja Abram ◽  
Sonja Smole Možina ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Mouse Liver ◽  
Virulence Genes ◽  
Cytokine Production ◽  
Host Responses ◽  
Human Origin ◽  
Tnf Α ◽  
Food Isolate ◽  
Ifn Γ ◽  
Food Model

 ABSTRACTObjective: Research into Campylobacter jejuni pathogenesis and host responses to C. jejuni infection is needed in the fight against human campylobacteriosis.Methods: We established intravenous infections of BALB/c mice with either a C. jejuni food isolate or C. jejuni of human origin. Further we include PCR to demonstrate the presence and stability of the putative virulence genes cadF, virbB11, cdtB, cdtC, ceuE in C. jejuni isolates and we examined cytokine production of IL-6, IL-12, TNF-α, IFN-γ, IL-10 in the livers of these infected mice.Results: We confirm here the presence of the cadF, cdtB, cdtC and ceuE genes in a food and a clinical C. jejuni isolate, with no sequence changes after the C. jejuni sub-culturing in a food model and when recovered from mouse liver after infection. Both of these C. jejuni isolates persisted in the mouse livers and activated comparable cytokine patterns for IL-12, TNF-α, IFN-γ and IL-10, with down-regulation of IL-6.Conclusions: These data show the comparability of these C. jejuni food and clinical isolates in terms of the prevalence and stability of their putative virulence genes and the outcome of disease during systemic murine campylobacteriosis.

scholarly journals Cytokine production by blood mononuclear cells from in-patients with anorexia nervosa

2002 ◽  
Vol 88 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Esther Nova ◽  
Sonia Gómez-Martínez ◽  
Gonzalo Morandé ◽  
Ascensión Marcos
Keyword(s):  
Anorexia Nervosa ◽  
Immune Function ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Protein Energy Malnutrition ◽  
Control Group ◽  
Control Subjects ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Although protein–energy malnutrition is a common cause of immunodeficiency, the immune function in underweight anorexia nervosa (AN) patients usually seems to be better preserved than would be expected. However, a deranged cytokine production and its consequences are currently being investigated in these patients. This study was aimed at measuring, over time, the capacity of peripheral blood mononuclear cells (PBMC) from AN in-patients to produce several cytokines involved in the regulation of immune responses. The in vitro production of interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α, IL-6 and IL-1β by phytohaemagglutinin-stimulated PBMC were assessed on forty female adolescents with AN. These measures were carried out twice, upon hospital admission and at discharge, which occurred on average after 1 month. Thirty-five control subjects were also studied. Cytokines were measured by ELISA kits. The production of TNF-α and IL-6 was lower and production of IL-1β higher in AN patients than in the control group at both time points of assessment. Refeeding for 1 month was not enough time to reverse these differences and patients still had a low body weight at discharge. IFN-γ production was lower in the patients than in control subjects only at discharge and no differences were found in IL-2 production between both groups. The results suggest that a mechanism involving modifications in the secretion pattern of proinflammatory cytokines could explain some immune function findings in underweight AN patients.

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