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TNF antagonist in childrens and infections

Erzhen Li, Yiyan Ruan, Qian Chen, Xiaodai Cui, Lingyun Lv, Ping Zheng, Liwen Wang
BACKGROUND: Streptococcal infection and basal ganglia inflammation are hypothesized to be involved in Tourette's syndrome (TS). There is a need for effective therapies for managing TS. We studied streptococcal infection and immunity in TS following immunomodulator (pidotimod) therapy. METHODS: Blood samples from 58 patients with TS and 128 age-matched healthy controls enabled measurement of antistreptolysin O (ASO), T cells, natural killer (NK) cells, interleukin-6 (IL-6) and interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α)...
July 2015: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Clara Giménez-Roca, Estíbaliz Iglesias, Vicenç Torrente-Segarra, Rosa Bou, Judith Sánchez-Manubens, Joan Calzada-Hernández, Samuel Hernández, Sílvia Ricart, Jordi Antón
The aims of the study were to assess efficacy and safety of TNF-alpha antagonists (anti-TNF) in a cohort of patients with juvenile idiopathic arthritis (JIA) who began treatment under 4 years old and to assess relapse rate after methotrexate and/or anti-TNF withdrawal. We made a retrospective charts review of our non-systemic JIA patients treated with anti-TNF under 4 years of age between January 2006 and April 2013. Demographics, epidemiologic, clinical, laboratory data and rate of relapse after treatment withdrawal due to clinical remission were collected...
February 2015: Rheumatology International
Andrea T Cruz, Lina B Karam, Robert C Orth, Jeffrey R Starke
Patients with inflammatory bowel disease are predisposed to opportunistic infections. We report 2 cases of disseminated tuberculosis in adolescents receiving a TNF antagonist, infliximab. Both had negative baseline tuberculin skin tests. Multimodal testing using tuberculin skin tests and interferon gamma release assays at the time of inflammatory bowel disease diagnosis and annually may increase the sensitivity of LTBI testing in these high risk children.
July 2014: Pediatric Infectious Disease Journal
David Gozal, Jinkwan Kim, Rakesh Bhattacharjee, Julie L Goldman, Leila Kheirandish-Gozal
BACKGROUND: Increased substance P (SP) levels and abundant expression of neurokinin (NK) 1 receptor in adenotonsillar tissues of children with OSA but not recurrent tonsillar infection (RI) suggest that NK1 antagonists could be useful in treating OSA. METHODS: The effects of SP and the NK1 antagonist GR-82334 were examined on mixed cell cultures prepared from dissociated tonsils harvested intraoperatively from children with OSA and RI. Proliferation was assessed by [3H]-thymidine or 5-ethynyl-2'-deoxyuridine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-1β) was assessed in supernatants by enzyme-linked immunosorbent assay...
May 2014: Chest
David Isaacs
Biologics are generally either custom-designed monoclonal antibodies against specific target cells (e.g. B-cells) or target cytokines (e.g. tumour necrosis factor, TNF) or they are receptor constructs (fusion proteins) based on naturally-occurring cytokine or cell receptors. Biologics are mostly used in adult rheumatology but are increasingly used in paediatrics. There are significant concerns about safety and also about cost. The main safety concerns are about increased risk of infection and malignancy. The use of TNF antagonists is associated with increased risk of serious infections with intracellular organisms, particularly mycobacteria, but also intracellular bacteria, fungi and Pneumocystis...
2013: Advances in Experimental Medicine and Biology
Prasad Rallabhandi, Rachel L Phillips, Marina S Boukhvalova, Lioubov M Pletneva, Kari Ann Shirey, Theresa L Gioannini, Jerrold P Weiss, Jesse C Chow, Lynn D Hawkins, Stefanie N Vogel, Jorge C G Blanco
UNLABELLED: Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Toll-like receptor 4 (TLR4), a signaling receptor for structurally diverse microbe-associated molecular patterns, is activated by the RSV fusion (F) protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner. TLR4 signaling by LPS also requires the presence of an additional protein, MD-2. Thus, it is possible that F protein-mediated TLR4 activation relies on MD-2 as well, although this hypothesis has not been formally tested...
2012: MBio
Judith Matz, Daniela L Krause, Sandra Dehning, Michael Riedel, Rudolf Gruber, Markus J Schwarz, Norbert Müller
BACKGROUND: Infections and immunological processes are likely to be involved in the pathogenesis of Tourette's syndrome (TS). To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. METHODS: In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex...
2012: BMC Psychiatry
Edward C Keystone
Given the important role tumor necrosis factor-α (TNF-α) antagonists play in managing rheumatoid arthritis and the concern for safety during longterm therapy, we reviewed the latest evidence regarding longterm risk of infection and malignancy with TNF-α antagonists. Our objective was to provide clinicians with information that can be used to counsel and monitor patients who may be candidates for biologic therapy for rheumatoid arthritis (RA). Risk is examined in the context of background infection and malignancy rates in RA...
August 2011: Journal of Rheumatology
I Solovic, M Sester, J J Gomez-Reino, H L Rieder, S Ehlers, H J Milburn, B Kampmann, B Hellmich, R Groves, S Schreiber, R S Wallis, G Sotgiu, E H Schölvinck, D Goletti, J P Zellweger, R Diel, L Carmona, F Bartalesi, P Ravn, A Bossink, R Duarte, C Erkens, J Clark, G B Migliori, C Lange
Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used...
November 2010: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Despina Eleftheriou, Tommy Gerschman, Neil Sebire, Patricia Woo, Clarissa A Pilkington, Paul A Brogan
OBJECTIVE: To date there is no uniformly effective treatment for either chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. We report on our clinical experience of using biologic therapy to treat children with these conditions. METHODS: Retrospective descriptive case series of four children with refractory disease treated with biologics. Disease activity was assessed at predetermined time points (T = 0, T = 6 weeks and T = 12 months after the start of biologic therapy, and at latest follow-up) using a combination of clinical examination and radiological findings: a 10 cm pain and physician visual analogue scale; the Childhood Health Assessment Questionnaire as an assessment of disability; and changes in markers of systemic inflammation...
August 2010: Rheumatology
Dan Fu, Cheng-rong Li, Yan-xia He, Ying Zu, De-zhi Cao, Guo-bing Wang, Ji-kui Deng, He-ping Wang
OBJECTIVE: To investigate the association of changes in immune function with enterovirus 71 (EV71) cases with different severity of the disease. METHOD: Forty-six EV71-infected patients and 12 age-matched healthy children were enrolled in this study. The patients were divided into four groups according to critical degree of enterovirus 71 infection: hand-foot-and-mouth disease (HFMD); central nervous system disease (CNSD); autonomic nervous system dysregulation (ANSD) and pulmonary edema (PE)...
November 2009: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Clare E Pain, Liza J McCann
Biologic agents have been designed with the help of immunological studies to target particular areas of the immune system which are thought to play a role in the pathogenesis of disease. Etanercept is a soluble anti-tumor necrosis factor alpha (TNF-alpha) agent licensed for the treatment of active poly-articular juvenile idiopathic arthritis (JIA) in children aged 4 to 17 years who have failed to respond to methotrexate alone, or who have been intolerant of methotrexate. The safety and efficacy of etanercept in this patient group has been established by one randomized controlled trial and several longitudinal studies...
2009: Biologics: Targets & Therapy
Chandy C John, Angela Panoskaltsis-Mortari, Robert O Opoka, Gregory S Park, Paul J Orchard, Anne M Jurek, Richard Idro, Justus Byarugaba, Michael J Boivin
Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF...
February 2008: American Journal of Tropical Medicine and Hygiene
Meredith L Allen, J Andreas Hoschtitzky, Mark J Peters, Martin Elliott, Allan Goldman, Ian James, Nigel J Klein
OBJECTIVE: A systemic insult is associated with subsequent hyporesponsiveness to endotoxin (as measured by ex vivo tumor necrosis factor [TNF]-alpha production) and an increased risk of late nosocomial infection in some patients. When combined with low monocyte surface major histocompatibility complex class II expression, this state of altered host defense is now commonly referred to as immunoparalysis. This study was undertaken to delineate the relationship between observed levels of the anti-inflammatory cytokine interleukin-10, common genetic polymorphisms that influence these levels, and the occurrence and severity of endotoxin hyporesponsiveness in children following elective cardiac surgery requiring cardiopulmonary bypass...
October 2006: Critical Care Medicine
Joseph Prandota
Prophylactic vaccinations may sometimes shorten the incubation period of some illnesses and/or convert a latent infection/inflammation into a clinically apparent disease. Cytokines play a major role in mediating the inflammatory process in various clinical entities and represent a potential source of tissue damage if their production is not sufficiently well controlled. It seems that irregularities in production of proinflammatory cytokines may be responsible for the abnormalities associated with full-blown clinical symptoms of various urinary tract diseases observed after DTP vaccination in 13 infants and young children hospitalized over the past 24 years...
September 2004: American Journal of Therapeutics
Judith Barash, Doron Dushnitzki, Yigal Barak, Shmuel Miron, Talia Hahn
Human parvovirus B19 (HPV) has been shown to be involved in the pathogenesis of various connective tissue and autoimmune diseases. In order to gain more information on HPV possible role in these diseases, we have investigated some immune responses in patients with acute HPV infection, mainly the secretion of the proinflammatory cytokine tumor necrosis factor (TNF)alpha and it's antagonist--the soluble TNF receptor (sTNFR) p75. Thirteen children with acute HPV infection and 13 healthy volunteers were investigated for the presence of autoantibodies, lymphocyte subpopulation counts, levels of total immunoglobulins, IgG subclasses and complement...
August 5, 2003: Immunology Letters
H Loppnow, E Westphal, R Buchhorn, A Wessel, K Werdan
Interleukin-1 (IL-1) is a key mediator in the cytokine network, controlling important functions in the immune system, during development, infection, inflammation, cell-differentiation, tissue remodelling, and even cell death. The agonistic isoforms of IL-1 (i.e., IL-1alpha and IL-1beta), the IL-1 receptor antagonists, the receptors and receptor-associated proteins, as well as the recently identified IL-18 and its receptor belong to the IL-1 family of proteins. Activation of the IL-1beta and IL-18 precursors is performed enzymatically by caspase-1, previously termed IL-1beta-converting enzyme (ICE)...
2001: Shock
B D Akanmori, J A Kurtzhals, B Q Goka, V Adabayeri, M F Ofori, F K Nkrumah, C Behr, L Hviid
The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than in the other clinical categories of P...
March 2000: European Cytokine Network
F Proulx, J P Turgeon, C Litalien, M M Mariscalco, P Robitaille, E Seidman
BACKGROUND: Recent experimental data suggest that the inflammatory response of the host to verotoxin and/or lipopolysaccharides of Escherichia coli is involved in the pathophysiology of verotoxin-producing E. coli (VTEC) infections. METHODS: We measured the circulating concentrations of cytokines [TNF-alpha, interleukin (IL)-1-beta, IL-1 receptor antagonist (Ra), IL-6, IL-8, IL-10] and soluble leukocyte adhesion molecules (L-selectin, P-selectin, E-selectin, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1) by sandwich enzyme-linked immunosorbent assay among (1) normal controls (n = 12), (2) disease controls with hemorrhagic colitis (HC) not associated with VTEC infections (n = 57), (3) patients with uncomplicated HC caused by E...
October 1998: Pediatric Infectious Disease Journal
A Nissan, J M Zhang, Z Lin, Y Haskel, H R Freund, M Hanani
Intussusception is a major cause for intestinal obstruction in children. Its etiology is unclear, but it is often associated with some kind of infection. We have developed a model for intussusception in mice using intraperitoneal (IP) injection of lipopolysaccharide (LPS). The objective of this study was to identify the putative mediators that participate in this LPS-induced intussusception. LPS (12 mg/kg) was injected into adult mice (N = 52) and 6 hr later, 25% of the animals demonstrated intussusception in the small or large intestine...
April 1997: Journal of Surgical Research
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