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Interleukin 1 receptor antagonist

Anthony S Wierzbicki, Timothy M Reynolds, Adie Viljoen
PURPOSE OF REVIEW: A number of novel trials have assessed the efficacy of new lipid-lowering therapies in cardiovascular disease (CVD). RECENT FINDINGS: Proprotein convertase subtilisin kexin-9 inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 50-55%. A CVD outcome trial in patients with acute coronary syndromes with evolocumab achieved a LDL-C of 0.8 mmol/l (31 mg/dl) and a 20% relative risk reduction in CVD events in 2.2 years. Cholesterol ester transfer protein inhibitors raise high-density lipoprotein cholesterol and can lower LDL-C...
March 19, 2018: Current Opinion in Cardiology
David P Perrault, Athanasios Bramos, Xingtian Xu, Songtao Shi, Alex K Wong
Impaired healing of the skin is a notable cause of patient morbidity and mortality. In diabetic individuals, dysregulated inflammation contributes to delayed wound healing. Specific immunomodulatory agents may have a role in the treatment of diabetic wounds. One of these molecules is interleukin-1 receptor antagonist (Anakinra; Amgen Corp.). Although interleukin-1 receptor antagonist (Anakinra; Amgen Corp.) is approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease, little is known about the local use this drug in cutaneous wound healing...
March 16, 2018: Annals of Plastic Surgery
Hyun Lee, Minoru Fujimoto, Tomoharu Ohkawara, Hiromi Honda, Satoshi Serada, Yoshio Terada, Tetsuji Naka
Recent evidence suggests that renal tubular injury plays a key role in deterioration of renal function in both chronic kidney disease (CKD) and acute kidney injury (AKI). Since commonly used biochemical indicators such as GFR, serum creatinine, blood urea nitrogen and creatinine clearance are inappropriate for detecting alteration in renal tubules, biomarkers reflecting renal tubular injury have been extensively explored. Our research group identified leucine rich α-2 glycoprotein (LRG) as a novel serum biomarker for various inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease...
March 16, 2018: Biochemical and Biophysical Research Communications
Xiaoxing Kou, Xingtian Xu, Chider Chen, Maria Laura Sanmillan, Tao Cai, Yanheng Zhou, Claudio Giraudo, Anh Le, Songtao Shi
Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs...
March 14, 2018: Science Translational Medicine
Alexandros Briasoulis, Chakradhari Inampudi, Mohan Pala, Rabea Asleh, Paulino Alvarez, Jay Bhama
Approximately 50% of heart transplant programs currently employ a strategy of induction therapy (IT) with either interleukin-2 receptor antagonists (IL2RA) or polyclonal anti-thymocyte antibodies (ATG) during the early postoperative period. However, the overall utility of such therapy is uncertain and data comparing induction protocols are limited. The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and through January 2018 for randomized controlled trials (RCTs) or observational controlled studies of IT vs no IT and IL2RA vs ATG...
March 13, 2018: Heart Failure Reviews
Peter M Grace, Xiaohui Wang, Keith A Strand, Michael V Baratta, Yingning Zhang, Erika L Galer, Hang Yin, Steven F Maier, Linda R Watkins
The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq - and Gi -coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which was abolished by intrathecal interleukin-1 receptor antagonist...
March 9, 2018: Experimental Neurology
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
BACKGROUND: Depressive disorders represent a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical inflammation increases the risk of depressive symptoms in the general population, but the relationship appears complex and bidirectional, and longitudinal data from patients with diabetes are lacking. Therefore, this study aimed to analyse associations between changes in depressive symptoms and changes in biomarkers of inflammation in patients with T1D and T2D and to investigate the hypothesis that higher baseline levels of biomarkers of inflammation are related to a less pronounced reduction of depressive symptoms over time...
March 6, 2018: Psychoneuroendocrinology
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
Subclinical inflammation has been implicated in the development of depression, a common comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). This study aimed to characterise the relationships between biomarkers of inflammation and depressive symptoms in T1D and T2D. Biomarkers of inflammation were measured in serum of participants with elevated depressive symptoms and T1D (n = 389, mean age 38 years, diabetes duration 15 ± 11 years) or T2D (n = 204, mean age 56 years, diabetes duration 13 ± 8 years)...
March 9, 2018: Translational Psychiatry
Minke H T Hartman, Hilde E Groot, Irene Mateo Leach, Jacco C Karper, Pim van der Harst
Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome...
February 15, 2018: Trends in Cardiovascular Medicine
A B Gottlieb, K Gordon, S Hsu, B Elewski, L F Eichenfield, L Kircik, S Rastogi, R Pillai, R Israel
BACKGROUND: Patients with psoriasis have lesional symptoms, including itch, which can reduce quality of life. The efficacy and safety of brodalumab, an interleukin-17 receptor A antagonist, in treating moderate-to-severe psoriasis have been reported in 3 randomized, controlled, phase 3 trials (AMAGINE-1/-2/-3). OBJECTIVE: The effect of brodalumab on lesional symptoms was assessed using the psoriasis symptom inventory (PSI), a validated patient-reported instrument...
March 6, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Carlene Petes, Mélissa K Mariani, Yawen Yang, Nathalie Grandvaux, Katrina Gee
Interleukin (IL)-30, the IL-27p28 subunit of the heterodimeric cytokine IL-27, acts as an antagonist of IL-27 and IL-6 signaling in murine cells via glycoprotein 130 (gp130) receptor and additional binding partners. Thus far, functions of IL-30 have not been fully elucidated in human cells. We demonstrate that like IL-27, IL-30 upregulated TLR4 expression to enhance lipopolysaccharide-induced TNF-α production in human monocytes; however, these IL-30-mediated activities did not reach the same levels of cytokine induction compared to IL-27...
2018: Frontiers in Immunology
Sílvia Castany, Georgia Gris, José Miguel Vela, Enrique Verdú, Pere Boadas-Vaello
Sigma-1 receptor (σ1 R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) - a model of central neuropathic pain. The modulatory effect of σ1 R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed...
March 1, 2018: Scientific Reports
Pablo Torres-Vergara, Jeffrey Penny
OBJECTIVES: The effects of anti-inflammatory glucocorticoids dexamethasone (DX) and hydrocortisone (HC), pro-inflammatory cytokine interleukin-1β (IL-1β) and dietary long-chain polyunsaturated fatty acids (PUFAs) on expression and activity of the ATP-binding cassette transporter P-glycoprotein (P-GP) were studied in porcine brain endothelial cells (PBECs). METHODS: Primary PBECs were treated for 24 h with glucocorticoids, IL-1β and long-chain PUFAs. P-GP activity was determined by measuring intracellular calcein accumulation and P-GP expression by Western blotting...
March 1, 2018: Journal of Pharmacy and Pharmacology
Cui Li, Yuan-Yuan Liu, Gui-Qiu Zhao, Jing Lin, Cheng-Ye Che, Nan Jiang, Na Li, Jie Zhang, Kun He, Xu-Dong Peng
AIM: To investigate the anti-inflammatory role of vasoactive intestinal peptide (VIP) in Aspergillus fumigatus ( A. fumigatus ) ketatitis. METHODS: Expression of VIP was tested by polymerase chain reaction (PCR) in C57BL/6 and BALB/c normal and A. fumigatus infected corneas. C57BL/6 mice were pretreated with recombinant (r) VIP, while BALB/c mice were pretreated with VIP antagonist, and then infected with A. fumigatus . Clinical score was recorded. Expression of pro- and anti-inflammatory cytokines, toll-like receptor 4 (TLR4), lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and neutrophil infiltration were tested by PCR, enzyme-linked immunosorbent assay (ELISA), and myeloperoxidase (MPO) assay...
2018: International Journal of Ophthalmology
Ruimeng Yang, Chong Duan, Liya Yuan, John A Engelbach, Christina I Tsien, Scott C Beeman, Carlos J Perez-Torres, Xia Ge, Keith M Rich, Joseph J H Ackerman, Joel R Garbow
PURPOSE: There is mounting evidence that, in addition to angiogenesis, hypoxia-induced inflammation via the hypoxia-inducible factor 1α (HIF-1α)-CXC chemokine receptor 4 (CXCR4) pathway may contribute to the pathogenesis of late-onset, irradiation-induced necrosis. This study investigates the mitigative efficacy of an HIF-1α inhibitor, topotecan, and a CXCR4 antagonist, AMD3100, on the development of radiation necrosis (RN) in an intracranial mouse model. METHODS AND MATERIALS: Mice received a single-fraction, 50-Gy dose of hemispheric irradiation from the Leksell Gamma Knife Perfexion and were then treated with either topotecan, an HIF-1α inhibitor, from 1 to 12 weeks after irradiation, or AMD3100, a CXCR4 antagonist, from 4 to 12 weeks after irradiation...
March 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Kijun Lee, Narae Park, Hyerin Jung, Yeri Alice Rim, Yoojun Nam, Jennifer Lee, Sung-Hwan Park, Ji Hyeon Ju
Human bone marrow-derived mesenchymal stem cells (MSCs) have been observed to inhibit arthritis in experimental animal models such as collagen-induced arthritis. However, the exact anti-inflammatory mechanisms remain poorly understood. Interleukin-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine produced by immune and stromal cells. We postulated that MSCs could produce IL-1Ra and attenuate experimental arthritis. In this study, 5x106 MSCs were injected into the peritoneal cavity of IL-1Ra knockout (IL-1RaKO) mice...
2018: PloS One
M N Karpenko, A A Vasilishina, E A Gromova, Z M Muruzheva, A Bernadotte
Several parameters representing the clinical diversity of Parkinson's disease (PD), including severity, phenotypes, cognitive decline, anxiety and depression were analyzed to examine the link with interleukin-1β (IL-1β), the interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-10, and tumor necrosis factor-α (TNFα) and also to determine the relationship between levels of these factors in serum and cerebrospinal fluid (CSF). Significantly elevated serum IL-1β and IL-6 and reduced IL-1RA levels were found in the PD group...
February 19, 2018: Cellular Immunology
Yun Zhang, Garth L Warnock, Ziliang Ao, Yoo Jin Park, Nooshin Safikhan, Aziz Ghahary, Lucy Marzban
Amyloid formation in the pancreatic islets due to aggregation of human islet amyloid polypeptide (hIAPP) contributes to reduced β-cell mass and function in type 2 diabetes (T2D) and islet transplantation. Protein kinase B (PKB) signaling plays a key role in the regulation of β-cell survival, function and proliferation. In this study, we used human and hIAPP-expressing transgenic mouse islets in culture as two ex vivo models of human islet amyloid formation to: 1. Investigate the effects of amyloid formation on PKB phosphorylation in primary islet β-cells; 2...
2018: PloS One
Fernanda Maria Martins, Aletéia de Paula Souza, Paulo Ricardo Prado Nunes, Márcia Antoniazi Michelin, Eddie Fernando Candido Murta, Elisabete Aparecida Mantovani Rodrigues Resende, Erick Prado de Oliveira, Fábio Lera Orsatti
OBJECTIVE: This study compared the effects of 12 weeks of high-intensity interval body weight training (HIBWT) with combined training (COMT; aerobic and resistance exercises on body composition, a 6-minute walk test (6MWT; physical performance), insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at high risk of type 2 diabetes mellitus (TDM2). METHODS: In this randomized controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated into two groups: HIBWT (n = 8) and COMT (n = 8)...
February 19, 2018: Experimental Gerontology
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