IMMUNE REGULATORY FUNCTION OF INTERFERON-GAMMA IN ACUTE LEUKEMIA

2021 ◽  
pp. 75-77
Author(s):  
Amit Choudhary
Keyword(s):  
Clinical Outcomes ◽  
Survival Rates ◽  
Regulatory Function ◽  
Minimal Impact ◽  
Immune Resistance ◽  
Solid Malignancies ◽  
Programmed Death ◽  
Tnf Α ◽  
Ifn Γ ◽  
Signaling Components

Programmed death ligand-1 (PDL-1) is an immune regulatory component that is expressed on normal cells, tumor cells, and non-tumor immune cells. The expression of these checkpoint components on the cell surface helps prevent the immune system's overactivity. PDL-1 is associated with immune evasion in many solid tumors and lymphomas, while its clinical signicance is under exploration in leukemias. Structural and regulatory aspects are recently presented in reports that dene the role of signaling components in regulating PDL-1. Immune interactions of soluble cytokines such as IFN-γ & TNF-α with PDL1 show relevance in liquid malignancies. Recent reports have shown that interaction occurs between IFN- γ and PDL 1, but the exact mechanism is not dened. PDL1 expression around 20-25% across the malignancies has put this immune checkpoint in clinical trials, and many solid malignancies have shown better clinical outcomes and survival rates. Still, resistance remains a signicant hurdle. Immune resistance is the primary reason for the minimal impact of PDL-1 blockade therapy in various cancers. IFN-γ induced PDL1 immunotherapy could be effective in leukemias to overcome the resistance and provide effective immune responses and overall better clinical outcomes.

scholarly journals Decreased plasma sPD-1 level correlates with disease activity in systemic juvenile idiopathic arthritis patients

2020 ◽  
Author(s):  
Li Cai ◽  
Chenxing Zhang ◽  
Ji Wu ◽  
Wei Zhou ◽  
Tongxin Chen
Keyword(s):  
Systemic Juvenile Idiopathic Arthritis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathophysiological Mechanism ◽  
Programmed Death ◽  
Tnf Α ◽  
Programmed Death 1 ◽  
Ifn Γ ◽  
Α Level ◽  
Inhibitor Treatment ◽  
Pro Inflammatory Cytokines

Abstract Objectives: Soluble programmed death-1 (sPD-1) and its ligand (sPD-L1) take part in some autoimmune diseases. Little is known about its role in systemic idiopathic arthritis (sJIA). The study aimed to explore the sPD-1 and sPD-L1 levels in sJIA patiens and elucidate their underlying immunomodulatory mechanisms. Methods: Plasma levels of sPD-1, sPD-L1 and related cytokines were detected in sJIA patients and healthy controls (HCs) using an enzyme-linked immunosorbent assay (ELISA) and Luminex. The correlation of sPD-1/sPD-L1 with clinical characteristics, laboratory parameters and pro-inflammatory cytokines level of patients were analyzed. The effects of PD-1/PD-L1 signal on T cell differentiation and IL-6 secretion were measured using flow cytometry. Results: The data revealed decreased levels of sPD-1 in active sJIA patients, and it negatively correlated with JADAS-27, PGA, PtGA and CRP. While the sPD-L1 level was positively correlated with Ferritin, S100A8, IL-6, IL-18, IL-1β and TNF-α level. Moreover, the sPD-1 and sPD-1/sPD-L1 could be sJIA diagnosis and IL-6R inhibitor treatment marker in patients. The vitro experiments showed that when blocking PD-1/PD-L1 signal, IFN-γ and IL-6 secretion were increased. Conclusions: Our finding displayed decreased sPD-1 in active sJIA patients, which could be a new biomarker for differential diagnosis and critical to further elucidating the pathophysiological mechanism of sJIA.

scholarly journals MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells

2017 ◽  
Vol 292 (50) ◽  
pp. 20683-20693 ◽  
Author(s):  
Daniel Yee ◽  
Kunal M. Shah ◽  
Mark C. Coles ◽  
Tyson V. Sharp ◽  
Dimitris Lagos
Keyword(s):  
Primary Cells ◽  
Programmed Death Ligand 1 ◽  
Human Primary Cells ◽  
Programmed Death ◽  
Tnf Α ◽  
Ifn Γ

Arsenic trioxide: a promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice

Blood ◽  
2006 ◽  
Vol 108 (13) ◽  
pp. 3967-3975 ◽  
Author(s):  
Pierre Bobé ◽  
Danielle Bonardelle ◽  
Karim Benihoud ◽  
Paule Opolon ◽  
Mounira K. Chelbi-Alix
Keyword(s):  
Nitric Oxide ◽  
Arsenic Trioxide ◽  
Therapeutic Agent ◽  
Fas Ligand ◽  
Survival Rates ◽  
Tnf Α ◽  
Activated T Lymphocytes ◽  
Ifn Γ ◽  
Kidney Lesions

Abstract MRL/lpr mice develop a human lupuslike syndrome and, as in autoimmune lymphoproliferative syndrome (ALPS), massive lymphoproliferation due to inactivation of Fas-mediated apoptosis. Presently, no effective therapy exists for ALPS, and long term, therapies for lupus are hazardous. We show herein that arsenic trioxide (As2O3) is able to achieve quasi-total regression of antibody- and cell-mediated manifestations in MRL/lpr mice. As2O3 activated caspases and eliminated the activated T lymphocytes responsible for lymphoproliferation and skin, lung, and kidney lesions, leading to significantly prolonged survival rates. This treatment also markedly reduced anti-DNA autoantibody, rheumatoid factor, IL-18, IFN-γ, nitric oxide metabolite, TNF-α, Fas ligand, and IL-10 levels and immune-complex deposits in glomeruli. As2O3 restored cellular reduced glutathione levels, thereby limiting the toxic effect of nitric oxide, which is overproduced in MRL/lpr mice. Furthermore, As2O3 protected young animals against developing the syndrome and induced almost total disease disappearance in older affected mice, thereby demonstrating that it is a novel promising therapeutic agent for autoimmune diseases.

scholarly journals Interleukin-12 Promotes Gamma Interferon-Dependent Neutrophil Recruitment in the Lung and Improves Protection against Respiratory Streptococcus pneumoniae Infection

2007 ◽  
Vol 75 (3) ◽  
pp. 1196-1202 ◽  
Author(s):  
Keer Sun ◽  
Sharon L. Salmon ◽  
Steven A. Lotz ◽  
Dennis W. Metzger
Keyword(s):  
Streptococcus Pneumoniae ◽  
Survival Rates ◽  
Gamma Interferon ◽  
Neutrophil Recruitment ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Innate Defense ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The ability of exogenous interleukin-12 (IL-12) to elicit protective innate immune responses against the extracellular pathogen Streptococcus pneumoniae was tested by infecting BALB/c mice intranasally (i.n.) with S. pneumoniae after i.n. administration of IL-12. It was found that administration of IL-12 resulted in lower bacterial burdens in the infected mice and significantly improved survival rates. All IL-12-treated mice contained higher levels of pulmonary gamma interferon (IFN-γ) after infection and significantly more neutrophils than infected mice not treated with IL-12. IFN-γ was found to be essential for IL-12-induced resistance and for neutrophil influx into the lungs, and the observed changes correlated with increased levels of the IL-8 homologue keratinocyte-derived chemokine (KC). In addition, in vitro tumor necrosis factor alpha (TNF-α) production by alveolar macrophages stimulated with heat-killed pneumococci was enhanced by IFN-γ, and TNF-α in turn could enhance production of KC by lung cells. Finally, IL-12-induced protection was dependent upon the presence of neutrophils and the KC receptor CXCR2. Taken together, the results indicate that exogenous IL-12 can improve innate defense in the lung against S. pneumoniae by inducing IFN-γ production, which in turn enhances chemokine expression, and promotes pulmonary neutrophil recruitment into the infected lung. The findings show that IL-12 and IFN-γ can mediate a protective effect against respiratory infection caused by extracellular bacterial pathogens.

scholarly journals Assessment of Interleukin-12, Gamma Interferon, and Tumor Necrosis Factor Alpha Secretion in Sera from Mice Fed with Dietary Lipids during Different Stages of Listeria monocytogenes Infection

2005 ◽  
Vol 12 (9) ◽  
pp. 1098-1103 ◽  
Author(s):  
María A. Puertollano ◽  
Lidia Cruz-Chamorro ◽  
Elena Puertollano ◽  
María T. Pérez-Toscano ◽  
Gerardo Álvarez de Cienfuegos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Listeria Monocytogenes ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Immune Resistance ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Recent experimental observations have determined that long-chain n-3 polyunsaturated fatty acids suppress immune functions and are involved in the reduction of infectious disease resistance. BALB/c mice were fed for 4 weeks with one of four diets containing either olive oil (OO), fish oil (FO), hydrogenated coconut oil, or a low fat level. Interleukin-12p70 (IL-12p70), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) production in the sera of mice fed these diets and challenged with Listeria monocytogenes were determined by enzyme-linked immunosorbent assay. In addition, bacterial counts from spleens of mice were carried out at 24, 72, or 96 h of infection. Here, we quantified an initial diminution of production of both IL-12p70 and IFN-γ, which appear to play an important role in the reduction of host resistance to L. monocytogenes infection. In addition, an efficient elimination of L. monocytogenes was observed in spleens of mice fed a diet containing OO at 96 h of infection, despite reductions in IL-12p70 and TNF-α production, suggesting an improvement of immune resistance. Overall, our results indicate that the initial reduction of both IL-12 and IFN-γ production before L. monocytogenes infection represents the most relevant event that corroborates the impairment of immune resistance by n-3 polyunsaturated fatty acids during the different stages of infection. However, we speculate that the modulation of other cytokines must be also involved in this response, because the alteration of cytokine production in mice fed an FO diet in a late phase of L. monocytogenes infection was similar to that in mice fed OO, whereas the ability to eliminate this bacterium from the spleen was improved in the latter group.

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