Targetting Interleukins Involved in Glioblastoma – A New Pharmacological Approach

Brain tumor is unchecked growth of brain cells disrupting many of its important functions and, affecting molecular regulatory and signaling networks. Glioblastoma is one of the most deleterious tumors of human brain. Cytokines are secondary messenger molecules in many of the immunological and other biochemical reactions. With glioblastoma progression, various cytokines are secreted that either up-regulate or down-regulate many others with immunological function. Interleukins are a family of cytokines acting mainly as immune-regulatory proteins. They have been implicated in brain tumor initiation, progression and invasion. Due to their multiple and varied regulatory roles at every stage of tumor, they are now becoming an attractive target for study in glioblastoma. This mini review briefly summarizes the types and roles of major interleukins and their regulation and, effects in glioblastoma that have been studied so far. Immunotherapeutic aspects are particularly emphasized as the promising therapeutic targets to control brain tumors. Main types of interleukins which are implicated in brain tumors are discussed here which includes interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-12 (IL-12). Glioblastoma is one of the most invasive tumor and still lack effective control measures clinically. Conventional treatments like chemotherapy and radiation therapy are not only ineffective in controlling the spread of glioblastoma, but also have damaging and unwanted side effects on healthy cells. Immunotherapy by blocking and/or increasing the action of certain interleukins has proven to be effective control measure in laboratory investigations. Future work extending these findings to clinical and human trials is expected to provide effective treatment measures.

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The Effect of Zearalenone on the Cytokine Environment, Oxidoreductive Balance and Metabolism in Porcine Ileal Peyer’s Patches

Toxins ◽

10.3390/toxins12060350 ◽

2020 ◽

Vol 12 (6) ◽

pp. 350

Author(s):

Kazimierz Obremski ◽

Wojciech Trybowski ◽

Paweł Wojtacha ◽

Magdalena Gajęcka ◽

Józef Tyburski ◽

...

Keyword(s):

Stress Responses ◽

Transforming Growth Factor ◽

Interleukin 2 ◽

Transforming Growth Factor Β ◽

Interleukin 10 ◽

Interferon Γ ◽

Basal Metabolism ◽

Interleukin 4 ◽

Interleukin 12 ◽

Factor Α

The aim of the present study was to determine the effect of zearalenone (ZEN), administered per os to gilts at doses equivalent to 50%, 100%, and 150% of no-observed-adverse-effect level (NOAEL) values for 14, 28, and 42 days during weaning, on changes in the parameters of the oxidoreductive balance, cytokine secretion, and basal metabolism in ileal Payer’s patches. Immunoenzymatic ELISA tests and biochemical methods were used to measure the concentrations of interleukin 1α, interleukin 1β, interleukin 12/23p40, interleukin 2, interferon γ, interleukin 4, interleukin 6, interleukin 8, tumor necrosis factor α, interleukin 10, transforming growth factor β, malondialdehyde, sulfhydryl groups, fructose, glucose, and proline, as well as the activity of peroxidase, superoxide dismutase and catalase. The study demonstrated that ZEN doses corresponding to 50%, 100%, and 150% of NOAEL values, i.e., 5 µg, 10 µg, and 15 µg ZEN/kg BW, respectively, have proinflammatory properties, exacerbate oxidative stress responses, and disrupt basal metabolism in ileal Payer’s patches in gilts.

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Serum Interleukin Profile in Patients with Graves Orbithopathy

Acta Medica Marisiensis ◽

10.2478/amma-2013-0007 ◽

2013 ◽

Vol 59 (1) ◽

pp. 31-35

Author(s):

Zsuzsánna Réti ◽

Iz Kun ◽

Corina Cristina Radu Pop

Keyword(s):

Disease Activity ◽

Interleukin 1 ◽

Interleukin 2 ◽

Interleukin 10 ◽

Interleukin 4 ◽

Disease Stage ◽

Clinical Activity ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ifn Γ

Abstract Background: Graves’ orbitopathy (GO) is considered an autoimmune condition in close relationship with Graves’ disease (GD) affecting the thyroid. Several similarities exist between the two conditions, sharing the common antigen and the characteristics of the inflammation mediated by a number of cytokines. The result of the immune reactions will lead to the expansion of adipose tissue, production of glycosaminoglycans and soft tissue inflammation. Material and methods: In our study we examined the serum level of interleukin-1 (IL-1), interleukin 2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in correlation with the activity of disease and smoking habits in 25 patients with GD and GO. Results: We found that smokers had higher serum IL-6 and lower serum MCP-1, IL-8 and TNF-α level compared to non-smokers. Also, we found a weak positive correlation between serum IL-10, IFN-γ and disease activity (clinical activity score, CAS) and negative correlation between serum IL-1 and activity. Conclusion: Our findings support the fact that some cytokines (IL-10, IFN-γ, IL-1) play a role in active disease, while others are influenced by environmental factors, such as smoking (IL-6, IL-8, TNF-α). The discrepancy of cytokine profiles may reflect different patient characteristics, such as disease stage and disease activity and determination of serum cytokines would be useful in selecting patients who need more aggressive treatment protocols.

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Interleukin‐4 regulation of human monocyte and macrophage interleukin‐10 and interleukin‐12 production. Role of a functional interleukin‐2 receptor γ‐chain

Immunology ◽

10.1046/j.1365-2567.1999.00711.x ◽

1999 ◽

Vol 96 (4) ◽

pp. 529-536 ◽

Cited By ~ 33

Author(s):

BONDER ◽

FINLAY‐JONES ◽

HART

Keyword(s):

Interleukin 2 ◽

Human Monocyte ◽

Interleukin 10 ◽

Interleukin 4 ◽

Interleukin 12 ◽

Interleukin 2 Receptor

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Characterizing the effectiveness of COVID-19 mitigation measures: A data-centric approach (Preprint)

10.2196/preprints.21321 ◽

2020 ◽

Author(s):

Lukman Olagoke ◽

Ahmet E. Topcu

Keyword(s):

Control Measure ◽

Control Measures ◽

World Health ◽

Mitigation Measures ◽

Effective Control ◽

The World ◽

Decision Making Processes ◽

And Performance ◽

Health Organization ◽

The Impact

BACKGROUND COVID-19 represents a serious threat to both national health and economic systems. To curb this pandemic, the World Health Organization (WHO) issued a series of COVID-19 public safety guidelines. Different countries around the world initiated different measures in line with the WHO guidelines to mitigate and investigate the spread of COVID-19 in their territories. OBJECTIVE The aim of this paper is to quantitatively evaluate the effectiveness of these control measures using a data-centric approach. METHODS We begin with a simple text analysis of coronavirus-related articles and show that reports on similar outbreaks in the past strongly proposed similar control measures. This reaffirms the fact that these control measures are in order. Subsequently, we propose a simple performance statistic that quantifies general performance and performance under the different measures that were initiated. A density based clustering of based on performance statistic was carried out to group countries based on performance. RESULTS The performance statistic helps evaluate quantitatively the impact of COVID-19 control measures. Countries tend show variability in performance under different control measures. The performance statistic has negative correlation with cases of death which is a useful characteristics for COVID-19 control measure performance analysis. A web-based time-line visualization that enables comparison of performances and cases across continents and subregions is presented. CONCLUSIONS The performance metric is relevant for the analysis of the impact of COVID-19 control measures. This can help caregivers and policymakers identify effective control measures and reduce cases of death due to COVID-19. The interactive web visualizer provides easily digested and quick feedback to augment decision-making processes in the COVID-19 response measures evaluation. CLINICALTRIAL Not Applicable

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Age-related aspects of cytokine profile of immune response in children with pertussis

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2020-65-3-84-90 ◽

2020 ◽

Vol 65 (3) ◽

pp. 84-90

Author(s):

O. P. Popova ◽

M. S. Blyakher ◽

I. M. Fedorova ◽

S. I. Koteleva ◽

I. V. Kapustin

Keyword(s):

Interleukin 2 ◽

Humoral Response ◽

Interleukin 10 ◽

Interferon Γ ◽

Interleukin 4 ◽

Cytokine Network ◽

Immunological Markers ◽

Age Related ◽

Immunoregulatory Cytokines ◽

The Relationship

The article presents a comparative analysis of the cytokine network in 161 patients with pertussis under the age of 1 year and in 180 patients over the age of 1 year. The studies revealed lower production of immunoregulatory cytokines (interferon-γ and interleukin-2) in patients under the age of 1 year at all stages of the disease and with all variants of pertussis (both mono- and mixed infections). The researchers revealed the relationship between the level of interferon-γ production and the severity of pertussis. They revealed age differences in the interferon-8 production in patients with mixed infection, which can determine clinical features and cause bronchopulmonary complications. The authors demonstrated the features of the dynamics of spontaneous and induced production of interleukin-6 and anti-inflammatory cytokines (interleukin-4, interleukin-10) in children under the age of 1 year; these features can be considered as immunological markers determining the imperfection of the humoral response in patients with pertussis in this age group.

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Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

International Journal of Inflammation ◽

10.1155/2014/856749 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Pramod Nehete ◽

Elizabeth R. Magden ◽

Bharti Nehete ◽

Patrick W. Hanley ◽

Christian R. Abee

Keyword(s):

Immune Function ◽

Inflammatory Cytokines ◽

Peptide Yy ◽

Interleukin 1 ◽

Interleukin 10 ◽

Interleukin 4 ◽

Low Grade ◽

Soluble Cd40 Ligand ◽

Killer Activity ◽

Metabolic Hormones

Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1βand anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γby PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

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Predisposition to Hyperthyroidism May Be Influenced by Functional TNF-α, IL-1, IL-6, and IL-10 Polymorphisms: A Meta-Analysis

International Archives of Allergy and Immunology ◽

10.1159/000508284 ◽

2020 ◽

Vol 181 (12) ◽

pp. 956-965

Author(s):

Hong Ma ◽

Ting Tan ◽

Jie Wu ◽

Juan Chen ◽

Xiaohong Zhang

Keyword(s):

Meta Analysis ◽

Interleukin 1 ◽

Interleukin 10 ◽

Interleukin 4 ◽

Asian Origin ◽

Tnf Α ◽

Caucasian Origin ◽

Meta Analyses ◽

Factor Α ◽

Necrosis Factor

Background: Predisposition to hyperthyroidism may be influenced by functional gene polymorphisms in tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). However, the results of the studies published so far remain discrepant, so we conducted a meta-analysis to more robustly investigate relationships between TNF-α/IL-1/IL-4/IL-6/IL-10 polymorphisms and predisposition to hyperthyroidism. Methods: A comprehensive literature retrieval from PubMed, Embase, Web of Science, WanFang, VIP, and CNKI was endorsed by the authors, and 38 studies were found to be eligible for pooled meta-analyses. Results: We found that genotypic frequencies of TNF-α −308 G/A, IL-1A −889 C/T, IL-6 −174 G/C, IL-6 −572 G/C, IL-10 −819 C/T, and IL-10 −1082 A/G polymorphisms among cases were significantly different from those among controls. Moreover, we also found that genotypic frequencies of TNF-α −308 G/A and IL-6 −174 G/C polymorphisms among cases of Caucasian origin were significantly different from those among Caucasian controls, and genotypic frequencies of IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −174 G/C, IL-6 −572 G/C, and IL-10 −1,082 A/G polymorphisms among cases of Asian origin were also significantly different from those among Asian controls. Conclusions: This meta-analysis suggests that TNF-α −308 G/A, IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −174 G/C, IL-6 −572 G/C, IL-10 −819 C/T, and IL-10 −1,082 A/G polymorphisms may influence predisposition to hyperthyroidism in certain ethnic groups.

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Response patterns of purified myeloma cells to hematopoietic growth factors

Blood ◽

10.1182/blood.v73.7.1915.1915 ◽

1989 ◽

Vol 73 (7) ◽

pp. 1915-1924 ◽

Cited By ~ 149

Author(s):

KC Anderson ◽

RM Jones ◽

C Morimoto ◽

P Leavitt ◽

BA Barut

Keyword(s):

Growth Factors ◽

Cell Lines ◽

Plasma Cell ◽

Plasma Cells ◽

Interleukin 1 ◽

Interleukin 2 ◽

Interleukin 4 ◽

Hematopoietic Growth Factors ◽

Myeloma Cells

Abstract Tumor cells were isolated from the bone marrow of seven patients with multiple myeloma and from the peripheral blood of three patients with plasma cell leukemia using Ficoll-Hypaque (FH) density sedimentation followed by immune rosette depletion of T, myeloid, monocytoid, and natural killer (NK) cells. Enrichment to greater than or equal to 93% plasma cells was confirmed with Wright's-Giemsa staining, with intracytoplasmic immunoglobulin staining, and with staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, monocytoid, and myeloma antigens in indirect immunofluorescence assays. Myeloma cells neither proliferated nor secreted Ig in response to G/M-CSF, G- CSF, M-CSF, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), or interleukin-4 (IL-4). Significant proliferation (SI greater than or equal to 3.0) was induced by interleukin-6 (IL-6) in six of ten patients (SI of 31 and 43 in two cases); and to interleukin-3 (IL-3) and interleukin-5 (IL-5), independently, in two patients each. Peak proliferation to IL-5 or IL-6 and to IL-3 occurred in cells pulsed with 3[H] thymidine at 24 and 48 hours, respectively; and proliferation to combinations of factors did not exceed that noted to IL-6 alone; Ig secretion was not documented under any culture conditions. Three myeloma-derived cell lines similarly studied demonstrated variable responses. The heterogeneity in the in vitro responses of myeloma cells and derived cell lines to exogenous growth factors enhances our understanding of abnormal plasma cell growth and may yield insight into the pathophysiology of plasma cell dyscrasias.

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