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Anti- cytokine therapies

Narcisa Martinez-Quiles, Raphaela Goldbach-Mansky
Autoinflammatory diseases are hyperinflammatory, immune dysregulatory diseases caused by innate immune cells dysregulation that present typically in the perinatal period with systemic and organ-targeted inflammation, but with improved genetic testing and the development of diagnostic criteria, milder and later-onset forms are being detected in adulthood. While the discovery of gain-of-function mutations in innate sensors linked to the production of proinflammatory cytokines provided the bases for anti-cytokine therapies that changed disease and patient outcomes, the field is expanding with the increasing discovery of disease-causing loss-of-function mutations in genes with cellular house-keeping functions that affect cell homeostasis and when dysregulated trigger innate inflammatory pathways...
November 16, 2018: Current Opinion in Immunology
Qiuju Han, Zhaohua Hou, Chunlai Yin, Cai Zhang, Jian Zhang
RNA with 5'-triphosphate (3p-RNA) is recognized by RNA sensor RIG-I (retinoic acid-inducible gene I protein). Previously, we reported that small interfering RNA targeting HBx (3p-siHBx) could confer potent anti-hepatitis B virus (HBV) efficacy via HBx silencing and RIG-I activation. However, the characteristics of innate and adaptive immunity especially exhaustion profiles in the liver microenvironment in response to 3p-siHBx therapy have not been fully elucidated. Here, we observed that 3p-siHBx more significantly inhibited HBV replication in vivo...
November 15, 2018: Antiviral Research
Jinxin Jiang, Qianqian Jian, Mei Jing, Zaijun Zhang, Gaoxiao Zhang, Luchen Shan, Pei Yu, Yuqiang Wang, Lipeng Xu
Acute lung injury (ALI) is a clinically severe respiratory disorder, and effective therapy is urgently needed. MN-08, a novel synthetic N-methyl-d-aspartate receptor (NMDAR) antagonist, was investigated for its effect on lipopolysaccharide (LPS)-induced ALI. In vitro, the protective effect of MN-08 on inflammatory response, oxidative stress, and tight junctions (TJs) structure was explored in LPS-induced RAW 264.7 cells and A549 cells. MN-08 markedly decreased (p < 0.001) the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), whereas it moderately upregulated (p < 0...
November 14, 2018: International Immunopharmacology
Li Teng Khoo, Liuh-Yow Chen
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway mediates anti-microbial innate immunity by inducing the production of type I interferons (IFNs) and inflammatory cytokines upon recognition of microbial DNA. Recent studies reveal that self-DNA from tumors and by-products of genomic instability also activates the cGAS-STING pathway and either promotes or inhibits tumor development. This has led to the development of cancer therapeutics using STING agonists alone and in combination with conventional cancer treatment or immune checkpoint targeting...
November 16, 2018: EMBO Reports
Rashmin C Savani
Over 50 years after its first description, Bronchopulmonary Dysplasia (BPD) remains a devastating pulmonary complication in preterm infants with respiratory failure and develops in 30-50% of infants less than 1000-gram birth weight. It is thought to involve ventilator- and oxygen-induced damage to an immature lung that results in an inflammatory response and ends in aberrant lung development with dysregulated angiogenesis and alveolarization. Significant morbidity and mortality are associated with this most common chronic lung disease of childhood...
October 2, 2018: Seminars in Perinatology
Kristine Oleinika, Claudia Mauri, Alan D Salama
B cells have a central role in many autoimmune diseases, including in those with renal involvement, as well as in the immunological response to kidney transplantation. The majority of B cell studies have focused on their pathological role as antibody producers. However, these cells have broad functions in immune responses beyond immunoglobulin secretion, including antigen presentation to T cells and cytokine production. Importantly, not all B cell subsets enhance immune responses. Regulatory B (Breg ) cells attenuate inflammation and contribute to the maintenance of immune tolerance...
November 15, 2018: Nature Reviews. Nephrology
Paola Vacca, Enrico Munari, Nicola Tumino, Francesca Moretta, Gabriella Pietra, Massimo Vitale, Genny Del Zotto, Francesca Romana Mariotti, Maria Cristina Mingari, Lorenzo Moretta
Innate lymphoid cells (ILC) including NK cells (cytotoxic) and the recently identified "helper" ILC1, ILC2 and ILC3, play an important role in innate defenses against pathogens. Notably, they mirror analogous T cell subsets, regarding the pattern of cytokine produced, while the timing of their intervention is few hours vs days required for T cell-mediated adaptive responses. On the other hand, the effectiveness of ILC in anti-tumor defenses is controversial. The relevance of NK cells in the control of tumor growth and metastasis has been well documented and they have been exploited in the therapy of high risk leukemia in the haploidentical hematopoietic stem cell transplantation setting...
November 12, 2018: Immunology Letters
Flávia Nathiely Silveira Fachel, Roselena Silvestri Schuh, Kleyton Santos Veras, Valquíria Linck Bassani, Letícia Scherer Koester, Amelia Teresinha Henriques, Elizandra Braganhol, Helder Ferreira Teixeira
Neurodegenerative disorders (ND) are characterized by slow and progressive neuronal dysfunction induced by the degeneration of neuronal cells in the central nervous system (CNS). Recently, the neuroprotective effects of natural compounds with anti-inflammatory and antioxidant activities has been clearly demonstrated. This appears to be an attractive therapeutic approach for ND, particularly regarding the use of polyphenols. In this review, we present an overview of the neuroprotective potential of rosmarinic acid (RA) and discuss the use of nanotechnology as a novel approach to treating ND...
November 12, 2018: Neurochemistry International
Katie L Greenwood, Jennifer H Foster
Dinutuximab, an anti-GD2 antibody, specifically targets the high-expression of GD2 on neuroblastoma cells, and its incorporation into maintenance high-risk neuroblastoma therapy has increased event-free survival for this devastating disease. Efficacy of dinutuximab during other phases of therapy or in relapsed and refractory patients remains under investigation. Areas covered: This review looked at available publications (via PubMed search and online abstract catalogues of recent scientific meetings) on pre-clinical safety studies of dinutuximab as well as results and current impressions of pending trials including dinutuximab and other anti-GD2 antibodies...
November 15, 2018: Expert Opinion on Drug Safety
Mumtaz Y Balkhi, Gabor Wittmann, Fang Xiong, Richard P Junghans
T cells infiltrate affected organs in chronic infections and malignancy, but they may fail to eradicate virus-infected cells or tumor because of exhaustion. This report describes a Yin Yang-1 (YY1)-centered mechanism for diverse components that have been correlated with exhaustion. Utilizing an in vitro reconstruction of chronic T cell activation, YY1 is shown to positively regulate the checkpoint receptors PD1, Lag3, and Tim3 and to negatively regulate the type I cytokines interleukin-2 (IL-2) (in collaboration with Ezh2 histone methyltransferase) and interferon gamma (IFN-?)...
April 27, 2018: iScience
Xinming Wang, Xiaoyun Chen, Wei Huang, Pengying Zhang, Yawei Guo, Heinrich Körner, Huaxun Wu, Wei Wei
The angiotensin II type 1 receptor (AT1R) antagonist losartan has been confirmed to have a moderate anti-inflammatory effect in vitro and in vivo. However, how it affects immune cells in Rheumatoid Arthritis (RA) is still unknown. We found that in human synovial tissues, AT1R is significantly expressed on T cells and B cells. Treatment with losartan (15 mg/kg) alone and in combination with a low dose of methotrexate (MTX 0.25 mg/kg/3 days) significantly suppressed the progression of CIA. Secondary paw swelling, joint destruction and the presence of pro-inflammatory cytokines (TNF-α and IFN-γ) in the serum were alleviated after treatment...
November 13, 2018: Inflammopharmacology
Yingzhan Tang, Guangyue Su, Ning Li, Wenjie Li, Gang Chen, Ru Chen, Di Zhou, Yue Hou
Our previous research revealed resin of Dracaena cochinchinensis as a candidate for therapy of neurodegenerative diseases. In the present study, the material basis of Chinese Dragon's blood and the primary mechanism of the effective components are discussed. Multiple chromatography and spectra analysis were utilized to identify effective constituents. The production of NO was determined using nitrite assay in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). Cell viability was tested using MTT assay...
November 13, 2018: Journal of Natural Medicines
Christopher J LaRocca, Susanne G Warner
Advances in the understanding of cancer immunotherapy and the development of multiple checkpoint inhibitors have dramatically changed the current landscape of cancer treatment. Recent large-scale phase III trials (e.g. PHOCUS, OPTiM) are establishing use of oncolytic viruses as another tool in the cancer therapeutics armamentarium. These viruses do not simply lyse cells to achieve their cancer-killing effects, but also cause dramatic changes in the tumor immune microenvironment. This review will highlight the major vector platforms that are currently in development (including adenoviruses, reoviruses, vaccinia viruses, herpesviruses, and coxsackieviruses) and how they are combined with checkpoint inhibitors...
November 14, 2018: Clinical and Translational Medicine
Justin Mastroianni, Natalie Stickel, Hana Andrlová, Kathrin Hanke, Wolfgang Melchinger, Sandra Duquesne, Dominik Schmidt, Martina Falk, Geoffroy Andrieux, Dietmar Pfeifer, Heide Dierbach, Annette Schmitt-Graeff, Frank Meiss, Melanie Boerries, Robert Zeiser
Micro-RNAs (miR) are small non-coding RNAs that regulate gene expression, post-transcription, and manipulate immune responses in different types of cancer. In this study, we identify miR-146a as a negative regulator of immune activation, comparable to immune checkpoint molecules. miR-146a levels were increased in melanoma microenvironmental tissue, and miR-146a-/- mice survived longer and developed less metastases in comparison to wild type melanoma-bearing mice. T cells isolated from miR-146a-/- mice revealed higher expression levels of the miR-146a target gene Stat1 and the Stat1-regulated cytokine Interferon-γ (IFN-γ)...
November 13, 2018: Cancer Research
Angelo Fassio, Davide Gatti, Maurizio Rossini, Luca Idolazzi, Alessandro Giollo, Giovanni Adami, Paolo Gisondi, Giampiero Girolomoni, Ombretta Viapiana
OBJECTIVES: Interleukin-17 (IL-17) is an important cytokine involved in the pathogenesis of bone lesions of psoriatic arthritis (PsA). The aim of our study was to explore the short-term effects (≤6 months) of secukinumab (an anti-IL-17 antibody) on the serum levels of bone turnover markers (BTMs) and on the inhibitors of the WNT signalling pathway. METHODS: The study sample consisted of patients with PsA starting treatment with secukinumab 150 mg every month, and healthy controls (HCs)...
October 23, 2018: Clinical and Experimental Rheumatology
Xuhui Hou, Songbai Yang, Yan Zheng
Licochalcone A (LA), a chalcone derived from liquorice, exhibits multiple biological activities, including anti-oxidation and anti-inflammation. This study aimed to investigate the role and underlying mechanism of LA in the abdominal aortic aneurysm (AAA). AAA model was established by continuous infusion of 1000 ng/kg/min of angiotensin II (AngII) in ApoE -/- mice for 4 weeks. At 7 days before AngII administration, 5 mg/kg/day or 10 mg/kg/day of LA was intraperitoneally administered to mice and continued for 4 weeks...
November 11, 2018: Journal of Cellular Physiology
Ronan O'Dwyer, Marina Kovaleva, Jiquan Zhang, John Steven, Emma Cummins, Deborah Luxenberg, Alfredo Darmanin-Sheehan, Miguel F Carvalho, Matthew Whitters, Kenneth Saunders, Caroline J Barelle
Lymphocyte costimulation plays a central role in immunology, inflammation, and immunotherapy. The inducible T cell costimulator (ICOS) is expressed on T cells following peptide: MHC engagement with CD28 costimulation. The interaction of ICOS with its sole ligand, the inducible T cell costimulatory ligand (ICOSL; also known as B7-related protein-1), triggers a number of key activities of T cells including differentiation and cytokine production. Suppression of T cell activation can be achieved by blocking this interaction and has been shown to be an effective means of ameliorating disease in models of autoimmunity...
2018: Journal of Immunology Research
Yusei Miyazaki, Masaaki Niino
Since the initial observation of increased immunoglobulin concentrations in the cerebrospinal fluid of patients with multiple sclerosis (MS) in the 1940s, B cells have been considered to participate in the pathology of MS through the production of autoantibodies reactive against central nervous system antigens. However, it is now recognized that B cells contribute to MS relapses by antibody-independent activities, including presenting antigens to T cells and releasing pro-inflammatory cytokines. In addition, the recent identification of B cell-rich follicle-like structures in the meninges of patients with MS suggests that pathogenic roles of B cells also exist at the progressive phase...
November 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
Mohamed I Husseiny, Weiting Du, Jacques Mbongue, Ayelet Lenz, Jeffrey Rawson, Fouad Kandeel, Kevin Ferreri
We previously reported the development of an oral vaccine for diabetes based on live attenuated Salmonella-expressing preproinsulin (PPI) as the autoantigen. When combined with host cell-expressed TGFβ, the vaccine prevented the onset of diabetes in non-obese diabetic (NOD) mice. Herein, we investigated factors that could affect vaccine efficacy including vaccination number, optimization of the autoantigen codon sequence, Salmonella SPI2-TTSS promoter/effector combinations, concurrent short-course low-dose anti-CD3...
November 8, 2018: Vaccine
Fatemeh Bina, Samaneh Soleymani, Tayebeh Toliat, Mannan Hajimahmoodi, Malihe Tabarrai, Mohammad Abdollahi, Roja Rahimi
Endometriosis is an estrogen-dependent disease with inflammatory lesions at extra-uterine sites, causing pelvic pain and fertility reduction. Conventional therapies primarily focus on reducing systemic levels of estrogens; however, they do not have desirable effectiveness and possess considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis. In this paper, electronic databases including PubMed, Scopus, Cochrane library and Google Scholar were searched to obtain any studies evaluating any herbal products in the management of endometriosis...
November 6, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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