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Sohei Oyama, Hidetomo Kitamura, Taichi Kuramochi, Yoshinobu Higuchi, Hiroaki Matsushita, Tsukasa Suzuki, Masaaki Goto, Hideki Adachi, Keiko Kasutani, Akihisa Sakamoto, Yuki Iwayanagi, Akihisa Kaneko, Masahiko Nanami, Etsuko Fujii, Keiko Esaki, Yoshiaki Takashima, Shin Shimaoka, Kunihiro Hattori, Yoshiki Kawabe
Scratching is an important factor exacerbating skin lesions through the so-called itch-scratch cycle in atopic dermatitis (AD). In mice, interleukin (IL)-31 and its receptor IL-31 receptor A (IL-31RA) are known to play a critical role in pruritus and the pathogenesis of AD; however, study of their precise roles in primates is hindered by the low sequence homologies between primates and mice and the lack of direct evidence of itch sensation by IL-31 in primates. We showed that administration of cynomolgus IL-31 induces transient scratching behavior in cynomolgus monkeys, and by that were able to establish a monkey model of scratching...
October 7, 2016: Experimental Dermatology
Carl D Richards, Laura Izakelian, Anisha Dubey, Grace Zhang, Steven Wong, Karen Kwofie, Aatif Qureshi, Fernando Botelho
IL-33 modulates both innate and adaptive immune responses at tissue sites including lung and may play critical roles in inflammatory lung disease. Although IL-33 expression can be altered upon NF-Kappa B activation, here we examine regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue. Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70...
2016: Mediators of Inflammation
Hitokazu Esaki, Patrick M Brunner, Yael Renert-Yuval, Tali Czarnowicki, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Donald B Johnson, Bruce Bauer, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xiangyu Peng, Yeriel D Estrada, Hui Xu, Christina de Guzman Strong, Mayte Suárez-Fariñas, James G Krueger, Amy S Paller, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD...
September 15, 2016: Journal of Allergy and Clinical Immunology
Bing Li, Huiting Su, Ju Cao, Liping Zhang
PURPOSE: To evaluate the expression and role of serum CXC chemokine ligand 13 (CXCL13) and cytokine IL-31 in hepatocellular carcinoma (HCC) patients. METHODS: A case-control study including preoperative serum samples of 78 patients with HCC, 78 patients with chronic hepatitis B (CHB) and 36 healthy controls (HCs) was conducted. The levels of serum CXCL13 and IL-31 were measured by enzyme-linked immunosorbent assays. The correlation of serum cytokines and clinical characteristics, laboratory parameters were analyzed retrospectively...
September 20, 2016: Cytokine
Gina M Michels, Deborah S Ramsey, Kelly F Walsh, Olivier M Martinon, Sean P Mahabir, Jacquelien D Hoevers, Rodney R Walters, Steven A Dunham
BACKGROUND: Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Lokivetmab, a caninized anti-canine IL-31 monoclonal antibody, reduced pruritus and associated inflammatory skin lesions in a proof-of-concept study in dogs with AD. HYPOTHESIS/OBJECTIVES: The objective was to describe lokivetmab dose response in a randomized, double blind, placebo-controlled trial. ANIMALS: Clinicians at 15 referral clinics enrolled 211 client owned dogs with a history of chronic AD...
September 19, 2016: Veterinary Dermatology
Gina M Michels, Kelly F Walsh, Kristina A Kryda, Sean P Mahabir, Rodney R Walters, Jacquelien D Hoevers, Olivier M Martinon
BACKGROUND: Lokivetmab (ZTS-00103289) is a caninized anti-canine IL-31 monoclonal antibody that has demonstrated efficacy in reducing pruritus associated with atopic dermatitis (AD) in dogs in field trials. HYPOTHESIS/OBJECTIVES: This study evaluated the safety of lokivetmab in a randomized, double blind, placebo-controlled trial in client owned dogs with AD with minimal restrictions on concomitant medications and co-morbidities. ANIMALS: Clinicians at 14 veterinary clinics enrolled client owned dogs (n = 245) with chronic AD...
September 19, 2016: Veterinary Dermatology
Hern-Tze Tina Tan, Kazunari Sugita, Cezmi A Akdis
PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP)...
October 2016: Current Allergy and Asthma Reports
Brijendra Singh, Anil G Jegga, Kumar S Shanmukhappa, Ramakrishna Edukulla, Gurjit H Khurana, Mario Medvedovic, Stacey R Dillon, Satish K Madala
Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis...
2016: PloS One
Amy S Paller, Yael Renert-Yuval, Maria Suprun, Hitokazu Esaki, Margeaux Oliva, Thy Nhat Huynh, Benjamin Ungar, Norma Kunjravia, Rivka Friedland, Xiangyu Peng, Xiuzhong Zheng, Yeriel D Estrada, James G Krueger, Keith A Choate, Mayte Suárez-Fariñas, Emma Guttman-Yassky
BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking, since the underlying molecular basis is poorly understood. OBJECTIVE: To characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsies from 21 genotyped ichthyosis patients (congenital ichthyosiform erythroderma (n=6), lamellar ichthyosis (n=7), epidermolytic ichthyosis, (n=5) and Netherton syndrome (n=3)) by immunohistochemistry and RT-PCR and compared them with healthy controls, and atopic dermatitis (AD) and psoriasis patients...
August 20, 2016: Journal of Allergy and Clinical Immunology
K E Lewis, M S Holdren, M F Maurer, S Underwood, B Meengs, S H Julien, K A Byrnes-Blake, J A Freeman, T R Bukowski, A C Wolf, N B Hamacher, M W Rixon, S R Dillon
BACKGROUND: Overexpression or administration of interleukin 31 (IL-31) has been shown to induce a profound itch response in mice and dogs. The chronic pruritus observed in mouse IL-31 transgenic mice results in the development of skin lesions and alopecia through excoriation from excessive scratching, a condition similar to that observed in patients with atopic dermatitis (AD). OBJECTIVE: To test whether IL-31 induces pruritus in non-human primates and, if so, whether treatment with an anti-IL-31 neutralizing monoclonal antibody (mAb) can block the response...
August 8, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Vanessa C Korb, Alisa Phulukdaree, Umesh G Lalloo, Anil A Chuturgoon, Devapregasan Moodley
T-helper (Th) 17 cells are a pro-inflammatory subset of CD4(+) effector T-cells critical in mucosal immunity. Imbalances in Th17 cell proportion have been implicated in the pathogenesis of several diseases; however, this has not been adequately explored in tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Since Th17 cells are predominantly mucosally associated, we assessed Th17 proportion and associated microenvironment in pleural effusions from patients co-infected with TB/HIV. Our results show that TB(+)HIV(+) pleurisy results in significantly reduced frequency of CD4(+)IL-17(+)RORC(+)STAT3(+) Th17 cells compared to TB(-)HIV(-)ex vivo (p = 0...
July 2016: Tuberculosis
F Basile, A Santamaria, C Mannucci, L Rizzo, S Gangemi, R D'anna, V Arcoraci
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder characterized by maternal itching and altered liver function. Interleukin (IL)-31 is known to be involved in the pathogenesis of pruritic inflammatory skin diseases. In a three-year period, 13 women with a singleton pregnancy and a diagnosis of intrahepatic cholestasis (ICP) were enrolled together with 26 healthy single pregnant women who concluded an uncomplicated pregnancy. The inclusion criteria were itching and elevated levels of liver transaminases...
July 13, 2016: Journal of Maternal-fetal & Neonatal Medicine
U Raap, E Papakonstantinou, M Metz, U Lippert, M Schmelz
The pathogenesis of chronic and acute pruritus is not yet completely understood. Interactions of neurons with resident and nonresident skin cells seem to play an important role in the regulation of pruritus. Neuronal cells which express specific receptors and are capable of releasing neuromediators play an active role in this interaction. Furthermore, released neuromediators can activate immune cells including mast cells and eosinophils, which are increased in the inflammatory infiltrate of many pruritic skin diseases...
August 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Xi Zeng, Zhu Zhang, Qian-Qian Gao, Yan-Yun Wang, Xiu-Zhang Yu, Bin Zhou, Ming-Rong Xi
Aims. Previous evidence has proved that interleukin-31 (IL-31) and interleukin-33 (IL-33) can be potential markers in some cancers' formulation. We aimed to determine the potential role of IL-31 and IL-33 in prognosis of endometrial cancer patients. Methods. Serum samples were collected from 160 patients with endometrial cancer and 160 healthy controls. The ELISA kits (Raybio® Systems) specific for human IL-31 and human IL-33 were used. Serum levels of tumor markers (CEA, CA-125, and CA19-9) were measured by chemiluminescence immunoassay...
2016: Disease Markers
Mayla Kezy Silva Teixeira, Ronaldo Lira-Junior, Daniel Moraes Telles, Eduardo José Veras Lourenço, Carlos Marcelo Figueredo
OBJECTIVE: This study aimed to compare Th17-related cytokines named IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in peri-implant fluid (PIF) from mucositis sites in patients having either peri-implantitis, periodontitis or without interproximal alveolar bone loss. MATERIAL AND METHODS: Thirty-three patients diagnosed with peri-implant mucositis were divided into three groups: individuals with peri-implant mucositis but without any signs of interproximal alveolar bone loss (group 1, n = 10), individuals with peri-implantitis (group 2, n = 14) and individuals with periodontitis (group 3, n = 9)...
June 9, 2016: Clinical Oral Implants Research
Magdalena Lange, Jolanta Gleń, Monika Zabłotna, Bogusław Nedoszytko, Małgorzata Sokołowska-Wojdyło, Krzysztof Rębała, Hanna Ługowska-Umer, Marek Niedoszytko, Aleksandra Górska, Monika Sikorska, Agata Zawadzka, Roman Nowicki
Data on interleukin-31 (IL-31) involvement in the patho-genesis of mastocytosis, and its impact on pruritus development in the disease, are limited. The aim of this study was to analyse distinct IL-31 gene polymorphisms in 127 patients (age 0.5-76 years) with mastocytosis and their correlation with clinical presentation, pruritus and serum IL-31 levels. In patients with mastocytosis, the frequency of IL-31 IVS2+12AA genotype and IVS2+12A allele was higher than in control subjects and they were linked to an increased risk of development of mastocytosis...
June 8, 2016: Acta Dermato-venereologica
Micha Feld, Richard Garcia, Jörg Buddenkotte, Shintaro Katayama, Katherine Lewis, Gareth Muirhead, Peter Hevezi, Kristin Plesser, Holger Schrumpf, Kaarel Krjutskov, Olga Sergeeva, Hans Werner Müller, Sophia Tsoka, Juha Kere, Stacey R Dillon, Martin Steinhoff, Bernhard Homey
BACKGROUND: Pruritus is a cardinal symptom of atopic dermatitis, and an increased cutaneous sensory network is thought to contribute to pruritus. Although the immune cell-IL-31-neuron axis has been implicated in severe pruritus during atopic skin inflammation, IL-31's neuropoietic potential remains elusive. OBJECTIVE: We sought to analyze the IL-31-related transcriptome in sensory neurons and to investigate whether IL-31 promotes sensory nerve fiber outgrowth. METHODS: In vitro primary sensory neuron culture systems were subjected to whole-transcriptome sequencing, ingenuity pathway analysis, immunofluorescence, and nerve elongation, as well as branching assays after IL-31 stimulation...
August 2016: Journal of Allergy and Clinical Immunology
U Nygaard, M Hvid, C Johansen, M Buchner, R Fölster-Holst, M Deleuran, C Vestergaard
BACKGROUND: Recent years have seen growing interest in identifying new biomarkers in atopic dermatitis (AD) that could serve as indicators of disease severity and predictors of treatment response. OBJECTIVES: We compared serum levels of thymic stromal lymphopoietin (TSLP), interleukin(IL)-31, IL-33 and soluble(s)ST2 in AD patients and healthy controls, investigated the possible correlation with disease severity, investigated if other atopic comorbidities could play a role, and assessed their potential as biomarkers in AD...
May 6, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Miranda S M Tsang, Delong Jiao, Ben C L Chan, Kam-Lun Hon, Ping C Leung, Clara B S Lau, Eric C W Wong, Ling Cheng, Carmen K M Chan, Christopher W K Lam, Chun K Wong
Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shubin Chong, Haimei Lan, Kang Zeng, Xuefeng Zhao
BACKGROUND: Atopic dermatitis (AD) is a common inflammatory allergic disease presenting pruritic skin lesions mainly in early childhood. Elevated fractalkine (FKN) expression is detected in AD patients. OBJECTIVE: We aimed to investigate the levels of FKN in serum and their association with disease severity in pediatric AD patients. METHODS: Serum samples were obtained from 57 AD children and 53 healthy children. Disease severity was assessed according to the following scoring systems: Leicester sign score (LSS), simple scoring system of costa (SSS), SCORing atopic dermatitis (SCORAD) index, and objective SCORAD...
2016: Annals of Clinical and Laboratory Science
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