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Cytokin storm

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
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
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...
March 7, 2018: Journal of Cellular and Molecular Medicine
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
Ganesh V Halade, Vasundhara Kain, Charles N Serhan
Resolvins are innate, immune responsive, bioactive mediators generated after myocardial infarction (MI) to resolve inflammation. The MI-induced bidirectional interaction between progressive left ventricle (LV) remodeling and kidney dysfunction is known to advance cardiorenal syndrome (CRS). Whether resolvins limit MI-induced cardiorenal inflammation is unclear. Thus, to define the role of exogenous resolvin D (RvD)-1 in post-MI CRS, we subjected 8-12-wk-old male C57BL/6 mice to coronary artery ligation. RvD1 was injected 3 h after MI...
February 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Diogo Kuczera, João Paulo Assolini, Fernanda Tomiotto-Pellissier, Wander Rogério Pavanelli, Guilherme Ferreira Silveira
Infection with dengue virus (DENV) can lead to a wide spectrum of clinical presentations, ranging from asymptomatic infection to death. It is estimated that the disease manifests only in 90 million cases out of the total 390 million yearly infections. Even though research has not yet elucidated which are the precise pathophysiological mechanisms that trigger severe forms of dengue, the infection elicits a critical immune response significant for dengue pathogenesis development. Understanding how the immune response to DENV is established and how it can resolve the infection or turn into an immunopathology is of great importance in DENV research...
February 2018: Journal of Interferon & Cytokine Research
Shingen Nakamura, Momoyo Azuma, Tomoko Maruhashi, Kimiko Sogabe, Ryohei Sumitani, Munenori Uemura, Masami Iwasa, Shiro Fujii, Hirokazu Miki, Kumiko Kagawa, Takashi Hiraga, Noriyasu Kondo, Hiromi Fujita, Fumihiko Mahara, Masahiro Abe
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women...
February 7, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Ji-Soo Kwon, Min-Chul Kim, Ji Yeun Kim, Na-Young Jeon, Byung-Han Ryu, Jeongmin Hong, Min-Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Sung-Han Kim
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Japan, and Korea, which is characterized by high fever, thrombocytopenia, and high mortality. It is hypothesized that a cytokine storm plays an important role in the pathophysiology of SFTS. However, limited data have been published on the detailed kinetics of the viral load and cytokine profiles throughout the course of this disease. OBJECTIVES: We investigated the patterns of changes in cytokines and viral load in SFTS patients...
January 31, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Dennis Wolf, Nathaly Anto-Michel, Hermann Blankenbach, Ansgar Wiedemann, Konrad Buscher, Jan David Hohmann, Bock Lim, Marina Bäuml, Alex Marki, Maximilian Mauler, Daniel Duerschmied, Zhichao Fan, Holger Winkels, Daniel Sidler, Philipp Diehl, Dirk M Zajonc, Ingo Hilgendorf, Peter Stachon, Timoteo Marchini, Florian Willecke, Maximilian Schell, Björn Sommer, Constantin von Zur Muhlen, Jochen Reinöhl, Teresa Gerhardt, Edward F Plow, Valentin Yakubenko, Peter Libby, Christoph Bode, Klaus Ley, Karlheinz Peter, Andreas Zirlik
Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo...
February 6, 2018: Nature Communications
Dar-In Tai, Wen-Juei Jeng, Chun-Yen Lin
Genome-wide association studies have indicated that human leukocyte antigen (HLA)-DP and HLA-DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV-related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis-related SNPs. We selected 12 HBV-related SNPs on the HLA locus and two HBV and three hepatitis C virus immune-related SNPs for analysis...
December 2017: Hepatology Communications
M Feuerecker, L Sudhoff, B Crucian, J-I Pagel, C Sams, C Strewe, A Guo, G Schelling, J Briegel, I Kaufmann, A Choukèr
The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered with (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °C in vitro with bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset...
January 29, 2018: Scientific Reports
Barun Poudel, Prajwal Gurung
Inflammasomes are multimeric protein complexes that promote inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. The central role of inflammasomes in combating infection and maintaining homeostasis has been studied extensively. Although inflammasome-mediated inflammation and cell death are vital to limit pathogenic insults and to promote wound healing/tissue regeneration, unchecked/uncontrolled inflammation, and cell death can cause cytokine storm, tissue damage, autoinflammatory and autoimmune diseases, and even death in the afflicted individuals...
January 26, 2018: Journal of Leukocyte Biology
Tessa van der Geest, Debbie M Roeleveld, Birgitte Walgreen, Monique M Helsen, Tapan K Nayak, Christian Klein, Martin Hegen, Gert Storm, Josbert M Metselaar, Wim B van den Berg, Peter M van der Kraan, Peter Laverman, Otto C Boerman, Marije I Koenders
Objectives: RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled anti-fibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis...
January 18, 2018: Rheumatology
Xihan Li, Zheng Fu, Hongwei Liang, Yanbo Wang, Xian Qi, Meng Ding, Xinlei Sun, Zhen Zhou, Ying Huang, Hongwei Gu, Limin Li, Xi Chen, Donghai Li, Quan Zhao, Fenyong Liu, Hua Wang, Jin Wang, Ke Zen, Chen-Yu Zhang
Infection of H5N1 influenza virus causes the highest mortality among all influenza viruses. The mechanisms underlying such high viral pathogenicity are incompletely understood. Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression...
January 12, 2018: Cell Research
Li-Fen Hu, Ting Wu, Bo Wang, Yuan-Yuan Wei, Qin-Xiang Kong, Ying Ye, Hua-Fa Yin, Jia-Bin Li
Severe fever with thrombocytopenia syndrome (SFTS) as an emerging infection disease results in high morbidity and mortality in China. In this study, the circulating levels of 36 inflammatory mediators in 33 SFTS patients on days 3-7, 8-12 and 13-20 post-illness were measured by a multiplex Luminex® system dynamically. Among the patients, 15 severe patients recovered, 11 severe patients died within three weeks. We found IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, eotaxin, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β and fractalkine were significantly upregulated in SFTS patients...
January 9, 2018: Scientific Reports
Nicola Mitwasi, Anja Feldmann, Ralf Bergmann, Nicole Berndt, Claudia Arndt, Stefanie Koristka, Alexandra Kegler, Justyna Jureczek, Anja Hoffmann, Armin Ehninger, Marc Cartellieri, Susann Albert, Claudia Rossig, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
As the expression of a tumor associated antigen (TAA) is commonly not restricted to tumor cells, adoptively transferred T cells modified to express a conventional chimeric antigen receptor (CAR) might not only destroy the tumor cells but also attack target-positive healthy tissues. Furthermore, CAR T cells in patients with large tumor bulks will unpredictably proliferate and put the patients at high risk of adverse side effects including cytokine storms and tumor lysis syndrome. To overcome these problems, we previously established a modular CAR technology termed UniCAR: UniCAR T cells can repeatedly be turned on and off via dosing of a target module (TM)...
December 12, 2017: Oncotarget
Hui Li, Konrad C Bradley, Jason S Long, Rebecca Frise, Jonathan W Ashcroft, Lorian C Hartgroves, Holly Shelton, Spyridon Makris, Cecilia Johansson, Bin Cao, Wendy S Barclay
The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load...
January 2018: PLoS Pathogens
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
Ellen Brisse, Maya Imbrechts, Tania Mitera, Jessica Vandenhaute, Carine H Wouters, Robert Snoeck, Graciela Andrei, Patrick Matthys
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder caused by unbridled activation of T cells and macrophages, culminating in a life-threatening cytokine storm. A genetic and acquired subtype are distinguished, termed primary and secondary HLH, respectively. Clinical manifestations of both forms are frequently preceded by a viral infection, predominantly with herpesviruses. The exact role of the viral infection in the development of the hemophagocytic syndrome remains to be further elucidated...
December 19, 2017: Virology Journal
John R Montford, Allison M B Lehman, Colin D Bauer, Jelena Klawitter, Jost Klawitter, Joanna M Poczobutt, Micah Scobey, Mary Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). WT C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice [WT-bone marrow transplant (BMT)] or mice deficient in cPLA2α (KO-BMT)...
February 2018: Journal of Lipid Research
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