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Cytokin storm

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https://www.readbyqxmd.com/read/29785126/impact-of-targeting-transforming-growth-factor-%C3%AE-2-with-antisense-ot-101-on-the-cytokine-and-chemokine-profile-in-patients-with-advanced-pancreatic-cancer
#1
Osmond J D'Cruz, Sanjive Qazi, Larn Hwang, Kevin Ng, Vuong Trieu
Background: Overexpression of the cytokine - transforming growth factor-beta 2 (TGF-β2) - has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-β2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-β receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29780651/fatal-outcome-of-imatinib-in-a-patient-with-idiopathic-hypereosinophilic-syndrome
#2
Ashraf Abugroun, Ahmed Chaudhary, Gabriel Rodriguez
Cytokine storm is a poorly explained clinical entity caused by an undesired and aggrandized immune system response leading to unregulated activation of the proinflammatory cascade, often contributing to multisystem organ failure and even death. Its potentially diverse etiologies and sepsis-like presentation have made it even more challenging to diagnose, and so far, no well-established treatment protocol has been proposed. Its association with certain medications, especially with monoclonal antibodies, has well been reported in literature...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29703874/cytokine-profile-of-patients-with-leptospirosis-in-sabah-malaysia
#3
B J Mohd Iskandar, T William, J Daisy Vanitha
BACKGROUND: Leptospirosis is a zoonotic disease with symptoms ranging from a mild, febrile illness to a severe form with multiorgan failure. Severe leptospirosis may require medical interventions in the form of dialysis and/or mechanical ventilation and often leads to mortality. An exaggerated host immune response-in particular, a "cytokine storm"-that causes endothelial and organ damage is associated with the disease severity and mortality. METHODS: Microscopic agglutination test (MAT)-positive and MAT-negative human serum samples (n=30) from patients with leptospirosis were obtained from the Public Health Laboratory, Kota Kinabalu, Sabah, Malaysia and control serum samples (n=10) were obtained from healthy student volunteers...
April 2018: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/29701145/a-potential-therapeutic-target-rna-binding-protein-arid5a-for-the-treatment-of-inflammatory-disease-associated-with-aberrant-cytokine-expression
#4
Kazuya Masuda, Tadamitsu Kishimoto
BACKGROUND: Infection, tissue damage and aging can cause inflammation with high levels of inflammatory cytokines. Overproduction of inflammatory cytokines often leads to systemic inflammatory response syndrome (SIRS), severe sepsis, and septic shock. However, prominent therapeutic targets have not been found, although the incidence of sepsis is likely to increase annually. Our recent studies indicate that some RNA-binding proteins, which control gene expression of inflammatory cytokines at the post-transcriptional level, may play a critical role in inflammatory diseases such as sepsis...
April 25, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29700351/cytokine-storms-are-primarily-responsible-for-the-rapid-death-of-ducklings-infected-with-duck-hepatitis-a-virus-type-1
#5
Jinyan Xie, Mingshu Wang, Anchun Cheng, Xin-Xin Zhao, Mafeng Liu, Dekang Zhu, Shun Chen, Renyong Jia, Qiao Yang, Ying Wu, Shaqiu Zhang, Yunya Liu, Yanling Yu, Ling Zhang, Kunfeng Sun, Xiaoyue Chen
Duck hepatitis A virus type 1 (DHAV-1) is one of the most harmful pathogens in the duck industry. The infection of adult ducks with DHAV-1 was previously shown to result in transient cytokine storms in their kidneys. To understand how DHAV-1 infection impacts the host liver, we conducted animal experiments with the virulent CH DHAV-1 strain and the attenuated CH60 commercial vaccine strain. Visual observation and standard hematoxylin and eosin staining were performed to detect pathological damage in the liver, and viral copy numbers and cytokine expression in the liver were evaluated by quantitative PCR...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29695416/deletion-of-inflammasome-components-is-not-sufficient-to-prevent-fatal-inflammation-in-models-of-familial-hemophagocytic-lymphohistiocytosis
#6
Sébastien Fauteux-Daniel, Sébastien Viel, Laurie Besson, Jiang Zhang, Marie Marotel, Anne-Laure Mathieu, Rémi Pescarmona, Emily Charrier, Thomas Henry, Alexandre Belot, Thierry Walzer
Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition that occurs in patients with genetic defects of cytotoxicity (familial HLH [FHL]) or secondary to other immunological disorders such as juvenile idiopathic arthritis. HLH is characterized by elevated levels of serum IL-18 and other cytokines. Moreover, a novel clinical entity has been recently identified in which constitutive NLRC4 inflammasome activation leads to severe HLH. Altogether, these clinical observations suggest that inflammasome activation is a central event in the development of all HLH forms and that inflammasome blockade could alleviate inflammation in FHL patients...
April 25, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29675946/plasma-proteomics-identifies-a-chemokine-storm-in-idiopathic-multicentric-castleman-disease
#7
Sheila K Pierson, Aaron J Stonestrom, Dustin Shilling, Jason Ruth, Christopher S Nabel, Amrit Singh, Yue Ren, Katie Stone, Hongzhe Li, Frits van Rhee, David C Fajgenbaum
Human Herpesvirus-8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) is a poorly understood disease involving polyclonal lymphoproliferation with dysmorphic germinal centers, constitutional symptoms, and multi-organ failure. Patients can experience thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly, and normal immunoglobulin levels, - iMCD-TAFRO. Others experience thrombocytosis, milder effusions, and hypergammaglobulinemia, -iMCD-Not Otherwise Specified (iMCD-NOS)...
April 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29664014/rip-kinase-1-dependent-endothelial-necroptosis-underlies-systemic-inflammatory-response-syndrome
#8
Matija Zelic, Justine E Roderick, Joanne A O'Donnell, Jesse Lehman, Sung Eun Lim, Harish P Janardhan, Chinmay M Trivedi, Manolis Pasparakis, Michelle A Kelliher
Receptor interacting protein kinase 1 (RIPK1) has important kinase-dependent and kinase-independent scaffolding functions that activate or prevent apoptosis or necroptosis in a cell context-dependent manner. The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF-induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory "cytokine storm" has long been viewed as detrimental. Here, we demonstrate that cytokine and chemokine levels did not predict survival and, importantly, that kinase-inactive Ripk1D138N/D138N hematopoietic cells afforded little protection from TNF- or TNF/zVAD-induced shock in reconstituted mice...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29643984/the-glucocorticoid-receptor-in-recipient-cells-keeps-cytokine-secretion-in-acute-graft-versus-host-disease-at-bay
#9
Tina Baake, Katharina Jörß, Jennifer Suennemann, Laura Roßmann, Hanibal Bohnenberger, Jan P Tuckermann, Holger M Reichardt, Henrike J Fischer, Sybille D Reichardt
Graft-versus-host disease (GvHD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), which is caused by allogeneic T cells recognizing molecules of the recipient as foreign. Endogenous glucocorticoids (GC) released from the adrenal gland are crucial in regulating such inflammatory diseases. Here we demonstrate that genetically engineered mice, that are largely unresponsive to GC, suffer from aggravated clinical symptoms and increased mortality after HSCT, effects that could be tempered by neutralization of IL-6...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29628283/weathering-the-storm-a-review-of-pre-pregnancy-stress-and-risk-of-spontaneous-abortion
#10
REVIEW
Tyralynn Frazier, Carol J Rowland Hogue, Elizabeth A Bonney, Kathryn M Yount, Brad D Pearce
The Weathering Effect is a theory that links stress exposure, over the life-course, with racial disparities in reproductive outcomes, through the effects of social adversity on a woman's body. The concept of maternal "weathering" captures cumulative somatic and psychological adversities that can exacerbate the effects of aging. Much of the evidence for weathering comes from observational studies linking self-report measures with reproductive outcomes. The purpose of this review is to explore biological mechanisms that underlie these observations...
March 1, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29620575/sphingosine-1-phosphate-receptor-2-signaling-promotes-caspase-11-dependent-macrophage-pyroptosis-and-worsens-escherichia-coli-sepsis-outcome
#11
Fang Song, Jinchao Hou, Zhecong Chen, Baoli Cheng, Ruyi Lei, Ping Cui, Yaqi Sun, Haihong Wang, Xiangming Fang
BACKGROUND: Pyroptosis, a type of proinflammatory programmed cell death, drives cytokine storm. Caspase-11-dependent macrophage pyroptosis contributes to mortality during sepsis. Sphingosine-1-phosphate receptor 2 (S1PR2) signaling can amplify interleukin-1β secretion in endotoxin-induced inflammation. Here, we hypothesized that S1PR2 signaling increases caspase-11-dependent macrophage pyroptosis and worsens Gram-negative sepsis outcome. METHODS: A Gram-negative sepsis model was induced through intraperitoneal injection of Escherichia coli...
April 3, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29616025/differences-between-pediatric-and-adult-t-cell-responses-to-in-vitro-staphylococcal-enterotoxin-b-stimulation
#12
Mark E Rudolph, Monica A McArthur, Robin S Barnes, Laurence S Magder, Wilbur H Chen, Marcelo B Sztein
Toxic shock syndrome (TSS) is capable of inducing life-threatening fever, rash, and systemic organ failure, though the specific mechanisms behind these symptoms remain poorly understood. Staphylococcal enterotoxin B (SEB) and other superantigens have shown to be important factors in TSS, capable of promoting cross-linking between T cell receptors and major histocompatibility complexes which results in overwhelming T cell activation, proliferation, and cytokine production. The resulting proinflammatory cytokine cascade, often referred to as the "cytokine storm," seems to be critical to the development of disease...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29597832/maternal-pufa-omega-3-supplementation-prevents-hyperoxia-induced-pulmonary-hypertension-in-the-offspring
#13
Ying Zhong, Daniel Catheline, Ali Houeijeh, Dyuti Sharma, Li-Zhong Du, Capucine Besengez, Philippe Deruelle, Philippe Legrand, Laurent Storme
Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25% of premature infants with bronchopulmonary dysplasia (BPD), contributing significantly to perinatal morbidity and mortality. Polyunsaturated fatty acids ω-3 (PUFA ω-3) can improve vascular remodeling, angiogenesis, and inflammation under pathophysiological conditions. However, the effects of PUFA ω-3 supplementation in BPD-associated PH are unknown. The present study aimed to evaluate the effects of PUFA ω-3 on pulmonary vascular remodeling, angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH...
March 29, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29577525/post-hematopoietic-stem-cell-transplant-hemophagocytic-lymphohistiocytosis-or-an-impostor-case-report-and-review-of-literature
#14
Anant Vatsayan, Irina Pateva, Linda Cabral, Jignesh Dalal, Rolla Abu-Arja
HLH occurring after HSCT is a relatively rare disease. Many conditions may mimic or trigger HLH in post-HSCT period (eg, cytokine release syndrome, engraftment syndrome, graft rejection/failure, acute graft-vs-host disease, infections systemic inflammatory response syndrome/sepsis, and thrombotic microangiopathy). Moreover, this period is usually marked by febrile illness, cytopenia, and a "cytokine storm" leading to elevation of inflammatory biomarkers like ferritin and sCD25. These parameters overlap with the diagnostic criteria for HLH...
March 25, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29563683/hemophagocytic-lymphohistiocytosis-in-an-infant-with-multiple-triggers
#15
Sataroopa Mishra, Amitabh Singh, Lavleen Singh, Anirban Mandal, Rahul Jain
Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune dysregulation secondary to a massive unregulated cytokine storm and its downstream consequences. HLH is being increasingly recognized as a cause of pyrexia of unknown origin, unexplained cytopenias, and hepatic dysfunction. However, this potentially treatable condition is often missed due to lack of suspicion, variable, and nonspecific presentations, inability to fulfil all the diagnostic criteria and availability of diagnostic tests in resource limited settings...
January 2018: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/29556253/the-importance-of-handling-high-value-biologicals-physico-chemical-instability-and-immunogenicity-of-monoclonal-antibodies
#16
REVIEW
Tomislav Laptoš, Jasna Omersel
The present review specifies the various chemical and physical factors that can influence drug stability and immunogenicity, and the treatment outcomes of antibody biologicals. Although monoclonal antibodies (mAbs) are known to be more resistant to environmental changes compared with other proteins, the molecules themselves can be subjected to chemical and physical processes that promote their degradation and transformation into their specific amino-acid moieties. With increasing use of medicinal products that contain mAbs, and their self-administration by the patients, the issue of the correct manipulation of these drugs is of increasing importance...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29515037/interleukin-7-restores-lymphocytes-in-septic-shock-the-iris-7-randomized-clinical-trial
#17
Bruno Francois, Robin Jeannet, Thomas Daix, Andrew H Walton, Matthew S Shotwell, Jacqueline Unsinger, Guillaume Monneret, Thomas Rimmelé, Teresa Blood, Michel Morre, Anne Gregoire, Gail A Mayo, Jane Blood, Scott K Durum, Edward R Sherwood, Richard S Hotchkiss
BACKGROUND: A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia...
March 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29513721/assessment-of-the-immunogenicity-of-residual-host-cell-protein-impurities-of-osrhsa
#18
Naghmeh Abiri, Jianlei Pang, Jiquan Ou, Bo Shi, Xianghong Wang, Sucai Zhang, Yunxia Sun, Daichang Yang
Human serum albumin (HSA) is the most abundant protein in human plasma and is widely used at high doses for treating various diseases. Recombinant HSA is an alternative approach to plasma-derived HSA, providing increased safety and an unlimited supply. However, the safety of the residual host cell proteins (HCPs) co-purified with Oryza sativa HSA (OsrHSA) remains to be determined. An animal system was used to assess the immunogenicity of OsrHSA and its residual HCPs. Low immunogenicity and immunotoxicity of the residual HCPs at a dose of 25 μg/kg, equivalent to 25 times the clinical dosage of HSA, were observed...
2018: PloS One
https://www.readbyqxmd.com/read/29512867/resveratrol-protects-mice-against-seb-induced-acute-lung-injury-and-mortality-by-mir-193a-modulation-that-targets-tgf-%C3%AE-signalling
#19
Hasan Alghetaa, Amira Mohammed, Muthanna Sultan, Philip Busbee, Angela Murphy, Saurabh Chatterjee, Mitzi Nagarkatti, Prakash Nagarkatti
Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by Staphylococcus aureus that triggers a strong immune response, characterized by cytokine storm, multi-organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB-driven ALI and mortality in mice. We used a dual-exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post-SEB exposure...
May 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29484126/retargeting-of-unicar-t-cells-with-an-in-vivo-synthesized-target-module-directed-against-cd19-positive-tumor-cells
#20
Dominik Bachmann, Roberta Aliperta, Ralf Bergmann, Anja Feldmann, Stefanie Koristka, Claudia Arndt, Simon Loff, Petra Welzel, Susann Albert, Alexandra Kegler, Armin Ehninger, Marc Cartellieri, Gerhard Ehninger, Martin Bornhäuser, Malte von Bonin, Carsten Werner, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
Recent treatments of leukemias with T cells expressing chimeric antigen receptors (CARs) underline their impressive therapeutic potential but also their risk of severe side effects including cytokine release storms and tumor lysis syndrome. In case of cross-reactivities, CAR T cells may also attack healthy tissues. To overcome these limitations, we previously established a switchable CAR platform technology termed UniCAR. UniCARs are not directed against typical tumor-associated antigens (TAAs) but instead against a unique peptide epitope: Fusion of this peptide epitope to a recombinant antibody domain results in a target module (TM)...
January 26, 2018: Oncotarget
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