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Cytokine release syndrome

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https://www.readbyqxmd.com/read/28237672/interleukin-10-a-compelling-therapeutic-target-in-patients-with-irritable-bowel-syndrome
#1
REVIEW
Sunil Kumar, Ratnakar Shukla, Prabhat Ranjan, Awanish Kumar
PURPOSE: Pro- and antiinflammatory cytokines are important modulators of the immune response and play a major role in conditions of intestinal inflammation, such as irritable bowel syndrome (IBS). Cytokine production is regulated genetically, and imbalances in cytokine secretion may affect disease susceptibility and clinical outcomes of various conditions. There is a rapidly growing body of evidence to support an etiologic role for gastrointestinal infection and the associated immune activation in the development of postinfectious IBS...
February 23, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28223167/intracavitary-t4-immunotherapy-of-malignant-mesothelioma-using-pan-erbb-re-targeted-car-t-cells
#2
Astero Klampatsa, Daniela Y Achkova, David M Davies, Ana C Parente-Pereira, Natalie Woodman, James Rosekilly, Georgina Osborne, Thivyan Thayaparan, Andrea Bille, Michael Sheaf, James F Spicer, Juliet King, John Maher
Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28218671/human-scfvs-that-counteract-bioactivities-of-staphylococcus-aureus-tsst-1
#3
Thunchanok Rukkawattanakul, Nitat Sookrung, Watee Seesuay, Nattawat Onlamoon, Pornphan Diraphat, Wanpen Chaicumpa, Nitaya Indrawattana
Some Staphylococcus aureus isolates produced toxic shock syndrome toxin-1 (TSST-1) which is a pyrogenic toxin superantigen (PTSAg). The toxin activates a large fraction of peripheral blood T lymphocytes causing the cells to proliferate and release massive amounts of pro-inflammatory cytokines leading to a life-threatening multisystem disorder: toxic shock syndrome (TSS). PTSAg-mediated-T cell stimulation circumvents the conventional antigenic peptide presentation to T cell receptor (TCR) by the antigen-presenting cell (APC)...
February 17, 2017: Toxins
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#4
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28196745/development-of-cell-based-assay-for-predictively-evaluating-the-fc%C3%AE-r-mediated-human-immune-cell-activation-by-therapeutic-monoclonal-antibodies
#5
Michiko Takakura, Minoru Tada, Akiko Ishii-Watabe
Therapeutic monoclonal antibodies (mAbs) have important roles in treatments for various cancers and inflammatory diseases. Their highly target specificities provide controlled safety profiles. However, therapeutic mAbs commonly pose a risk of the induction of the release of cytokines, which may result in adverse events including infusion reaction and cytokine release syndrome. Several mechanisms are involved in the cytokine releases induced by therapeutic mAbs, and the activation of immune effector cells via Fcγ receptors (FcγRs) is one of the putative mechanisms for most IgG-subclass mAbs...
February 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28191008/the-nlrp3-and-pyrin-inflammasomes-implications-in-the-pathophysiology-of-autoinflammatory-diseases
#6
REVIEW
Carlos de Torre-Minguela, Pablo Mesa Del Castillo, Pablo Pelegrín
Inflammasomes are multiprotein complexes that critically control different aspects of innate and adaptive immunity. Among them we could highlight the release of pro-inflammatory cytokines that induce and maintain the inflammatory response. Usually, inflammasomes result from oligomerization of a nucleotide-binding domain-like receptor (NLR) after sensing different pathogenic or endogenous sterile dangerous signals; however, other proteins such as absent in melanoma 2, retinoic acid-inducible gene I, or pyrin could also form inflammasome platforms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28187946/inducible-caspase-9-selectively-modulates-the-toxicities-of-cd19-specific-chimeric-antigen-receptor-modified-t-cells
#7
Iulia Diaconu, Brandon Ballard, Ming Zhang, Yuhui Chen, John West, Gianpietro Dotti, Barbara Savoldo
Immunotherapy with T cells expressing the chimeric antigen receptor (CAR) specific for the CD19 antigen (CD19.CAR-Ts) is a very effective treatment in B cell lymphoid malignancies. However, B cell aplasia and cytokine release syndrome (CRS) secondary to the infusion of CD19.CAR-Ts remain significant drawbacks. The inclusion of safety switches into the vector encoding the CAR is seen as the safest method to terminate the effects of CD19.CAR-Ts in case of severe toxicities or after achieving long-term sustained remissions...
February 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28179388/disseminated-intravascular-coagulation-like-reaction-following-rituximab-infusion
#8
Hind Rafei, Samah Nassereddine, Ivan F Garcia
Rituximab generally is a well-tolerated medication used in a variety of haematological and autoimmune conditions. The safety profile of the medication has been reviewed in the literature. Infusion reactions due to cytokine release are the most common side effects. With the increased use of rituximab, there is an increase incidence of cytopenias, most commonly thrombocytopenia and leucopenia. Coagulopathy is quite rare, reported previously in four cases in the literature. We highlighted the clinical course of a 39-year-old patient with precursor B-cell acute lymphoblastic leukaemia who was started on rituximab infusion...
February 8, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28176955/urinary-excretion-of-il-1%C3%AE-il-6-and-il-8-cytokines-during-relapse-and-remission-of-idiopathic-nephrotic-syndrome
#9
Amal A Al-Eisa, Maysoun Al Rushood, Rajaa J Al-Attiyah
BACKGROUND/AIM: The role of pro-inflammatory cytokines in the immunopathogenesis of idiopathic nephrotic syndrome had been widely postulated. Reports on the release of cytokines, during idiopathic nephrotic syndrome (INS) activation, were conflicting in defining a specific interleukin pattern during relapse and remission of the disease. The aim of this study was to explore the role of IL-1β, IL-6 and IL-8 in the pathophysiology of INS during relapse and remission. PATIENTS AND METHODS: A total of 37 INS patients were included...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28153725/differences-in-the-effects-of-four-trpv1-channel-antagonists-on-lipopolysaccharide-induced-cytokine-production-and-cox-2-expression-in-murine-macrophages
#10
Yuki Ninomiya, Sei-Ichi Tanuma, Mitsutoshi Tsukimoto
Sepsis is a systemic inflammatory response syndrome triggered by lipopolysaccharide (LPS), an outer membrane component of gram-negative bacteria, and cytokine production via LPS-induced macrophage activation is deeply involved in its pathogenesis. Effective therapy of sepsis has not yet been established. However, it was reported that transient receptor potential vanilloid 1 (TRPV1) channel antagonist capsazepine (CPZ; a capsaicin analogue) attenuates sepsis in a murine model [Ang et al., PLoS ONE 6(9) (2011) e24535; J...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28129747/giardia-specific-cellular-immune-responses-in-post-giardiasis-chronic-fatigue-syndrome
#11
Kurt Hanevik, Einar Kristoffersen, Kristine Mørch, Kristin Paulsen Rye, Steinar Sørnes, Staffan Svärd, Øystein Bruserud, Nina Langeland
BACKGROUND: The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue...
January 28, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28129122/phase-1-results-of-zuma-1-a-multicenter-study-of-kte-c19-anti-cd19-car-t-cell-therapy-in-refractory-aggressive-lymphoma
#12
Frederick L Locke, Sattva S Neelapu, Nancy L Bartlett, Tanya Siddiqi, Julio C Chavez, Chitra M Hosing, Armin Ghobadi, Lihua E Budde, Adrian Bot, John M Rossi, Yizhou Jiang, Allen X Xue, Meg Elias, Jeff Aycock, Jeff Wiezorek, William Y Go
Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m(2)) and fludarabine (30 mg/m(2)) for 3 days followed by KTE-C19 at a target dose of 2 × 10(6) CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary endpoint...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129120/targeting-of-aberrant-%C3%AE-v%C3%AE-6-integrin-expression-in-solid-tumors-using-chimeric-antigen-receptor-engineered-t-cells
#13
Lynsey M Whilding, Ana C Parente-Pereira, Tomasz Zabinski, David M Davies, Roseanna M G Petrovic, Y Vincent Kao, Shobhit A Saxena, Alex Romain, Jose A Costa-Guerra, Shelia Violette, Hiroaki Itamochi, Sadaf Ghaem-Maghami, Sabari Vallath, John F Marshall, John Maher
Expression of the αvβ6 integrin is upregulated in several solid tumors. In contrast, physiologic expression of this epithelial-specific integrin is restricted to development and epithelial re-modeling. Here, we describe, for the first time, the development of a chimeric antigen receptor (CAR) that couples the recognition of this integrin to the delivery of potent therapeutic activity in a diverse repertoire of solid tumor models. Highly selective targeting αvβ6 was achieved using a foot and mouth disease virus-derived A20 peptide, coupled to a fused CD28(+)CD3 endodomain...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28128714/donor-origin-car-t-cells-graft-versus-malignancy-effect-without-gvhd-a-systematic-review
#14
Faiz Anwer, Al-Aman Shaukat, Umar Zahid, Muhammad Husnain, Ali McBride, Daniel Persky, Melissa Lim, Nida Hasan, Irbaz Bin Riaz
CD19, CD20 chimeric antigen receptor T (CAR T) cell therapy has shown promising results for the treatment of relapsed or refractory hematological malignancies. Best results have been reported in acute lymphoblastic leukemia patients with a complete response rate above 80%. Patients who received donor-derived CAR T cells for the relapsed malignancy after stem cell transplantation (allogenic hematopoietic stem cell transplant) were identified from the published trials. A total of 72 patients from seven studies were treated with donor-derived CAR T cells...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/28126984/vaccination-to-improve-the-persistence-of-cd19car-gene-modified-t-cells-in-relapsed-pediatric-acute-lymphoblastic-leukemia
#15
C Rossig, M Pule, B Altvater, S Saiagh, G Wright, S Ghorashian, L Clifton-Hadley, K Champion, Z Sattar, B Popova, A Hackshaw, P Smith, T Roberts, E Biagi, B Dreno, R Rousseau, S Kailayangiri, M Ahlmann, R Hough, B Kremens, M G Sauer, P Veys, N Goulden, M Cummins, P J Amrolia
Trials with 2nd generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but associated with risk of Cytokine Release Syndrome (CRS). Instead, we studied use of donor Epstein Barr virus-specific T-cells (EBV CTL) transduced with a 1st generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi- center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric ALL. Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10-4) post-1st SCT, or prophylactically post-2nd SCT...
January 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28120605/hemophagocytic-lymphohistiocytosis-mimics-many-common-conditions-case-series-and-review-of-literature
#16
A T Akenroye, N Madan, F Mohammadi, J Leider
Introduction. Hemophagocytic lymphohistiocytosis (HLH), a rare but potentially fatal disease, is characterized by excessive immune activation and cytokine release which stimulates bone marrow macrophages to engulf hematopoietic cells. HLH could be secondary to infections: viral, fungal, and bacterial; malignancies and autoimmune diseases. The diagnosis of HLH is usually delayed due to the presence of non-specific symptoms at presentation. This delay contributes to increased mortality. Cases and review. We present the case of 4 patients who presented with subjective fevers and extreme fatigue...
January 2017: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28112391/mesenchymal-stem-cells-improves-survival-in-lps-induced-acute-lung-injury-acting-through-inhibition-of-nets-formation
#17
Leonardo Pedrazza, Aline Andrea Cunha, Carolina Luft, Nailê Karine Nunes, Felipe Schimitz, Rodrigo Benedetti Gassen, Ricardo Vaz Breda, Marcio Vinícius Fagundes Donadio, Angela Terezinha de Souza Wyse, Paulo Marcio Condessa Pitrez, Jose Luis Rosa, Jarbas Rodrigues de Oliveira
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxigen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28110056/current-knowledge-and-management-of-hypersensitivity-reactions-to-monoclonal-antibodies
#18
Matthieu Picard, Violeta Régnier Galvão
Hypersensitivity reactions (HSRs) to monoclonal antibodies (mAbs) are increasingly frequent as this class of therapeutic agents is rapidly expanding. Immediate and nonimmediate HSRs have been reported with mAbs. Immediate HSRs can be explained by 3 main mechanisms: cytokine release syndrome, IgE-mediated, and IgG-mediated reactions. Importantly, IgE-mediated reactions can occur on first exposure due to preformed specific IgEs, as shown for cetuximab. Almost all patients with an immediate HSR can be safely re-exposed either through desensitization or challenge depending on the severity and mechanism of the initial reaction...
January 18, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28104514/increased-foxp3-helios-regulatory-t-cells-and-decreased-acute-graft-versus-host-disease-after-allogeneic-bone-marrow-transplantation-in-patients-receiving-sirolimus-and-rgi-2001-an-activator-of-invariant-natural-killer-t-cells
#19
Yi-Bin Chen, Yvonne A Efebera, Laura Johnston, Edward D Ball, David Avigan, Lazaros J Lekakis, Carlos R Bachier, Paul Martin, Omar Duramad, Yasuyuki Ishii, Semi Han, Yu-Jin Jung, Dana Lee, Lori Kunkel, Robert S Negrin, Jack D Bui
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells...
January 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28098913/diets-link-metabolic-syndrome-and-colorectal-cancer-development-review
#20
Jirakrit Saetang, Surasak Sangkhathat
Diets have been believed to be an important factor in the development of metabolic syndrome and colorectal cancer (CRC). In recent years, many studies have shown an intimate relationship between mucosal immunity, metabolism and diets, which has led to a greater understanding of the pathophysiology of metabolic syndrome and CRC development. Although the precise effects of diets on oncogenesis have not been compl-etely elucidated, microbiota changes and inflammation are believed to be important factors that influence the development of CRC...
January 18, 2017: Oncology Reports
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