DOCSLIB.ORG

High Interleukin-10 Serum Levels Are Associated with Fatal Outcome in Patients After Bone Marrow Transplantation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
High Interleukin-10 Serum Levels Are Associated with Fatal Outcome in Patients After Bone Marrow Transplantation Bone Marrow Transplantation, (1997) 20, 365–368 1997 Stockton Press All rights reserved 0268–3369/97 $12.00 High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation L Hempel1,DKo¨rholz2, P Nußbaum3,HBo¨nig2, S Burdach2,4 and F Zintl1 1Department of Pediatric Hematology and Oncology, Friedrich-Schiller University Medical Center, Jena; 2Department of Pediatric Hematology and Oncology, Heinrich-Heine University Medical Center, Du¨sseldorf; 3Institute of Clinical Pathology, Osnabru¨ck; and 4Biomedical Research Center, Heinrich-Heine University, Du¨sseldorf, Germany Summary: production.1–3 Experiences with IL-10 knock-out mice show that IL-10 may contribute to the control of inflamma- IL-10 plays an important role in the control of immune tory reactions because these animals showed severe gastro- reactions during systemic infection. Here, IL-10 serum intestinal inflammation.4 In mouse models, elevation of IL- levels were investigated in patients after BMT. The IL- 10 during systemic infection protected the animals from 10 levels correlated with the clinical course of the an overwhelming immune reaction. Furthermore, mice with patients and with serum levels of C-reactive protein high endogenous or exogenous IL-10 levels survived sys- (CRP) and neopterin (NP). A total of 26 patients with temic shock syndromes, while application of anti-IL-10 led AML (7), ALL (12), CML (2), NHL (3) and multifocal to a fatal reaction.5–7 In contrast, in humans elevated IL-10 Ewing’s sarcoma (2) had received autologous (10) or levels during systemic shock correlated with an increased allogeneic (16) BMT from related (9) or unrelated TNF-a production, increased severity of septic shock and donors (7). Routine serum samples were obtained prior a high risk of disseminated intravascular coagulation.8–10 to BMT and at days 46 and 100 after BMT. However, The association between high IL-10 levels and fatality of in patients with severe complications additional samples septic shock was explained by the fact that IL-10 might not were drawn at individual points in time. Prior to BMT, be able to inhibit production of proinflammatory cytokines, IL-10 serum levels were not detectable in 24/24 patients. while suppressing T cell reactions which might otherwise Post-BMT, 11 patients developed elevated IL-10 levels, have supported pathogen elimination. In this study the role of these eight died of complications (DOC), whereas of IL-10 in patients after BMT was investigated under the only one of 15 patients with undetectable IL-10 died of hypothesis that in post-BMT patients, as in sepsis, complications, indicating that high IL-10 levels were sig- increased IL-10 might be correlated to poor outcome. IL- nificantly correlated with severe life-threatening compli- 10 serum levels correlated with the clinical course of the cations (x2, P , 0.01). To determine the pathomechan- disease, the severity of acute phase reactions and macro- ism and role of the increased IL-10 levels, they were phage activation. correlated to the respective NP and CRP serum concen- trations. CRP and NP concentrations were found sig- nificantly elevated in patients with detectable IL-10, Patients and methods indicating a severe acute phase reaction associated with Patients macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associa- Twenty-six children and adolescents were enrolled into this ted with fatal outcome. Since IL-10 is a strong sup- study. Patients’ ages ranged from 4.0 to 22.4 years (median: pressor of T cell immunity, high IL-10 production in 13.4 years). The male to female ratio was 18 to 8. Patients patients with severe complications such as septic shock had previously been treated for ALL (12), AML (7), CML or GVHD .grade II after BMT might lead to functional (2), NHL (3) and Ewing’s sarcoma (2). Five patients had immunodeficiency contributing to the poor prognosis of received an allogeneic transplant from a matched-related these patients. donor, four patients had been transplanted with bone mar- Keywords: sepsis; bone marrow transplantation; inter- row from an haploidentical related donor and seven patients leukin 10; neopterin had had unrelated donors. In addition, 10 patients had received autologous bone marrow or peripheral blood stem cell transplants. Blood was drawn from patients prior to BMT and at days 46 and 100 after BMT. However, in IL-10 is a potent macrophage and T cell-deactivating patients with multi-organ failure (MOF) additional blood cytokine, leading to a significant suppression of cytokine samples were taken during these complications. At the time of study, all patients with allogeneic transplants received immunosuppressive treatment. Acute GVHD was seen in Correspondence: L Hempel, Department of Pediatric Hematology and Oncology, Friedrich-Schiller University Medical Center, Kochstr 2, D- only six of 16 patients (Table 1). However, six of 10 07740 Jena, Germany patients without acute GVHD died in the early post-trans- Received 21 March 1997; accepted 15 May 1997 plant period. Interleukin-10 and bone marrow transplantation L Hempel et al 366 Table 1 Patients characteristics No. Initials Sex Age Diagnosis Status at BMT Type of transplant Acute GVHD Status 1 DH F 17.2 ALL CR matched related GVHD II CCR 2 AK M 14.6 CML PR matched related none CCR 3 DS M 14.7 ALL CR matched related none DOC, day +67 4 KS M 4.0 ALL CR matched related none CCR 5 FT M 11.5 AML CR matched related none relapse day +126, died day +183 6 CK M 14.6 CML PR matched unrelated none DOC, day +34 7 RK M 8.7 AML relapse matched unrelated none DOC, day +20 8 CK M 10.4 NHL PR matched unrelated none DOC, day +26 9 SM F 7.1 ALL CR matched unrelated GVHD I–II CCR 10 KR F 22.4 ALL relapse matched unrelated none DOC, day +27 11 SR M 18.1 AML CR matched unrelated GVHD III DOC, day +103 12 FZ M 17.4 AML relapse matched unrelated none DOC, day +21 13 TB F 11.2 ALL CR mismatched related GVHD II CCR 14 CL F 10.8 ALL CR mismatched related GVHD II CCR 15 NS M 13.7 ALL relapse mismatched related GVHD II–III DOC, day +83 16 CS F 14.3 ALL relapse mismatched related none DOC, day +19 17 RB M 12.8 AML CR autologous none relapse day +293, alive 18 RF M 19.9 ALL CR autologous none relapse day +192, died day +220 19 EG M 17.7 AML CR autologous none CCR 20 MG M 17.9 NHL CR autologous none CCR 21 BH F 7.5 ALL CR autologous none CCR 22 HH M 17.5 AML CR autologous none CCR 23 DS M 15.4 EWS PR autologous none relapse day +161, alive 24 JS F 11.0 EWS PR autologous none CCR 25 NS M 7.3 NHL CR autologous none CCR 26 PW M 12.8 ALL CR autologous none CCR The study was performed in accordance with the ethical Statistical analysis of data standards laid down in the 1964 Declaration of Helsinki. 2 Patients or their parents gave their consent. The study was The Wilcoxon and x tests were used for statistical analysis. authorized by the local ethics committee. Results Cytokine analysis Concentrations of IL-10 were assessed by commercially To determine the role of IL-10 in patients after BMT, IL- available ultrasensitive ELISA kits (BioSource, Camarillo, 10 serum levels were correlated with the clinical course of CA, USA) as described previously.3 The lowest concen- the patients. Prior to BMT (‘day 0’) serum levels of IL- tration detected by this assay was 200 fg/ml. 10 were undetectable in all patients. Post-BMT 11 patients developed detectable IL-10 at various points in time. Of these, eight patients died of complications within 1–14 Neopterin (NP) determination (median 4) days after an elevated IL-10 had been found. The three surviving patients with elevated IL-10 serum lev- Serum neopterin levels were measured by HPLC. Briefly, els presented with acute GVHD grade II or severe CMV 200 ml samples or standards were added to a mobile phase infection. One patient received systemic IL-2 treatment at containing 0.1 m KH2PO4, (Merck, Darmstadt, Germany), the time of IL-10 determination. In 15/26 patients IL-10 0.005 m octansulfonic acid (Fluka, Bux, Switzerland; pH remained undetectable throughout the observation period. was adjusted to 3.0 with 1 N HCl) and 50 ml of 3.4 m Of these, only one succumbed to complications. The last HClO4. After vortexing the mixtures for 30 s, samples were IL-10 measurement in this patient had been done 21 days centrifuged at 11 500 r.p.m. for 5 min. Supernatants (50 ml) prior to his death so that an increased IL-10 may have been were applied to a HPLC (Li-Chros-Pher 100 RP 8E; missed. Thus, we found detectable IL-10 levels to be sig- Merck). Neopterin concentrations were determined at Ex nificantly correlated with DOC (Figure 1; Table 2; x2, wavelength of 360 nm compared with Em wavelength of P , 0.01). 430 nm. Next, the mechanism of in vivo IL-10 production was investigated. It was found that in patients with detectable CRP determination IL-10, CRP levels (median: 8.57 mg/dl) were significantly elevated as compared to patients with undetectable IL-10 CRP values were determined by particle-enhanced immu- (median: 0 mg/l; Figure 2, Wilcoxon test, P , 0.001). nonephelometry. 40 ml serum were applied to a fully auto- Thus, in our patient population the IL-10 serum levels were matic nephelometer (Behringwerke, Marburg, Germany).
Load more

Recommended publications
  • Genetic Determinants of Circulating Interleukin-1 Receptor Antagonist Levels and Their Association with Glycemic Traits
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Trepo - Institutional Repository of Tampere University GENETIC DETERMINANTS OF CIRCULATING INTERLEUKIN-1 RECEPTOR ANTAGONIST LEVELS AND THEIR ASSOCIATION WITH GLYCEMIC TRAITS Marja-Liisa Nuotio Syventävien opintojen kirjallinen työ Tampereen yliopisto Lääketieteen yksikkö Tammikuu 2015 Tampereen yliopisto Lääketieteen yksikkö NUOTIO MARJA-LIISA: GENETIC DETERMINANTS OF CIRCULATING INTERLEUKIN-1 RECEPTOR ANTAGONIST LEVELS AND THEIR ASSOCIATION WITH GLYCEMIC TRAITS Kirjallinen työ, 57 s. Ohjaaja: professori Mika Kähönen Tammikuu 2015 Avainsanat: sytokiinit, insuliiniresistenssi, tyypin 2 diabetes, tulehdus, glukoosimetabolia, genominlaajuinen assosiaatioanalyysi (GWAS) Tulehdusta välittäviin sytokiineihin kuuluvan interleukiini 1β (IL-1β):n kohonneen systeemisen pitoisuuden on arveltu edesauttavan insuliiniresistenssin kehittymistä ja johtavan haiman β-solujen toimintahäiriöihin. IL-1β:n sisäsyntyisellä vastavaikuttajalla, interleukiini 1 reseptoriantagonistilla (IL-1RA), on puolestaan esitetty olevan suojaava rooli mainittujen fenotyyppien kehittymisessä päinvastaisten vaikutustensa ansiosta. IL-1RA:n suojaavan roolin havainnollistamiseksi työssä Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits tunnistettiin veren IL-1RA- pitoisuuteen assosioituvia geneettisiä variantteja, minkä jälkeen selvitettiin näiden yhteyttä glukoosi- ja insuliinimetaboliaan liittyvien muuttujien-, sekä
    [Show full text]
  • The Comparison of Interleukin-17 and Interleukin-10 with Systemic Lupus Erythematosus Disease Activity
    Scientific Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Aug 25; 8(B):793-797. https://doi.org/10.3889/oamjms.2020.4782 eISSN: 1857-9655 Category: B - Clinical Sciences Section: Rheumatology The Comparison of Interleukin-17 and Interleukin-10 with Systemic Lupus Erythematosus Disease Activity Dwitya Elvira1, Iris Rengganis1*, Rudy Hidayat2, Hamzah Shatri3 1Division of Allergy and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine University of Indonesia- Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 2Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine University of Indonesia-Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Division of Psychosomatic and Palliative Medicine, Department of Internal Medicine, Faculty of Medicine University of Indonesia-Cipto Mangunkusumo Hospital, Jakarta, Indonesia Abstract Edited by: Slavica Hristomanova-Mitkovska AIM: This study was conducted to compare means of interleukin-17 (IL-17) (Th17 cytokines) and interleukin-10 Citation: Elvira D, Rengganis I, Hidayat R, Shatri H. The Comparison of Interleukin-17 and Interleukin-10 with (IL-10) (T-regulatory cytokines) as pro-inflammatory and anti-inflammatory cytokine with disease activity of systemic Systemic Lupus Erythematosus Disease Activity. Open lupus erythematosus (SLE) and to investigate correlation between IL-17 cytokine serums with IL-10 in SLE patients. Access Maced J Med Sci. 2020 Aug 25; 8(B):793-797. https:// doi.org/10.3889/oamjms.2020.4782 METHODS: This study recruited total of 68 SLE patients which included 34 active and 34 inactive patients based Keywords: Interleukin-17; Interleukin-10; Systemic lupus erythematosus; Disease activity on MEX-SLEDAI as disease activity tool measurement and subjects were selected using consecutive sampling *Correspondence: Iris Rengganis, Division of Allergy and method.
    [Show full text]
  • Inflammation-Induced IL-6 Functions As a Natural Brake On
    BASIC RESEARCH www.jasn.org Inflammation-Induced IL-6 Functions as a Natural Brake on Macrophages and Limits GN Michael Luig,* Malte A. Kluger,* Boeren Goerke,* Matthias Meyer,* Anna Nosko,* † ‡ † Isabell Yan, Jürgen Scheller, Hans-Willi Mittrücker, Stefan Rose-John,§ Rolf A.K. Stahl,* Ulf Panzer,* and Oliver M. Steinmetz* *Medical Clinic III and †Immunology Institute, Hamburg University Medical Center, Hamburg, Germany; ‡Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and §Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany ABSTRACT IL-6 can mediate proinflammatory effects, and IL-6 receptor (IL-6R) blockade as a treatment for in- flammatory diseases has entered clinical practice. However, opposing effects of IL-6 have been observed in models of GN. Although IL-6 is proinflammatory in murine lupus nephritis, protective effects have been observed for IL-6 in the nephrotoxic nephritis (NTN) model of acute crescentic GN. In light of the potential dangers of IL-6–directed treatment, we studied the mechanisms underlying the contradictory findings in GN. IL-6 can signal through the membrane-bound IL-6R, which is expressed only on hepatocytes and certain leukocytes (classic), or through the soluble IL-6R, which binds the ubiquitously expressed gp130 (alternative). Preemptive treatment of mice with anti-IL-6R or anti-IL-6 worsened NTN, whereas selective blockade of alternative IL-6 signaling by the fusion protein sgp130Fc did not. FACS analysis of mouse spleen cells revealed proinflammatory macrophages express the highest levels of IL-6Ra,andin vitro treatment with IL-6 blocked macrophage proliferation. Furthermore, proinflammatory macrophages were 2 2 expanded during inflammation in IL-6 / mice.
    [Show full text]
  • Comprehensive Association Study of Genetic Variants in the IL-1 Gene Family in Systemic Juvenile Idiopathic Arthritis
    Genes and Immunity (2008) 9, 349–357 & 2008 Nature Publishing Group All rights reserved 1466-4879/08 $30.00 www.nature.com/gene ORIGINAL ARTICLE Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis CJW Stock1, EM Ogilvie1, JM Samuel1, M Fife1, CM Lewis2 and P Woo1 1Centre for Paediatric and Adolescent Rheumatology, Windeyer Institute for Medical Sciences, University College London, London, UK and 2Guy’s, Kings and St Thomas’ School of Medicine, London, UK Patients with systemic juvenile idiopathic arthritis (sJIA) have a characteristic daily spiking fever and elevated levels of inflammatory cytokines. Members of the interleukin-1 (IL-1) gene family have been implicated in various inflammatory and autoimmune diseases, and treatment with the IL-1 receptor antagonist, Anakinra, shows remarkable improvement in some patients. This work describes the most comprehensive investigation to date of the involvement of the IL-1 gene family in sJIA. A two-stage case–control association study was performed to investigate the two clusters of IL-1 family genes using a tagging single nucleotide polymorphism (SNP) approach. Genotyping data of 130 sJIA patients and 151 controls from stage 1 highlighted eight SNPs in the IL1 ligand cluster region and two SNPs in the IL1 receptor cluster region as showing a significant frequency difference between the populations. These 10 SNPs were typed in an additional 105 sJIA patients and 184 controls in stage 2. Meta-analysis of the genotypes from both stages showed that three IL1 ligand cluster SNPs (rs6712572, rs2071374 and rs1688075) and one IL1 receptor cluster SNP (rs12712122) show evidence of significant association with sJIA.
    [Show full text]
  • Evolutionary Divergence and Functions of the Human Interleukin (IL) Gene Family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W
    UPDATE ON GENE COMPLETIONS AND ANNOTATIONS Evolutionary divergence and functions of the human interleukin (IL) gene family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W. Nebert3* and Vasilis Vasiliou1 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected]; [email protected] Date received (in revised form): 22nd September 2010 Abstract Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term ‘interleukin’ (IL) has been used to describe a group of cytokines with complex immunomodulatory functions — including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host’s immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type.
    [Show full text]
  • Inducing Cytokines − and IL-10 Inhibits IL-17 Response by Eliciting
    The Journal of Immunology The TLR7 Ligand 9-Benzyl-2-Butoxy-8-Hydroxy Adenine Inhibits IL-17 Response by Eliciting IL-10 and IL-10–Inducing Cytokines Alessandra Vultaggio,*,1 Francesca Nencini,†,‡,1 Sara Pratesi,†,‡ Laura Maggi,†,‡ Antonio Guarna,x Francesco Annunziato,†,‡ Sergio Romagnani,†,‡ Paola Parronchi,†,‡ and Enrico Maggi†,‡ This study evaluates the ability of a novel TLR7 ligand (9-benzyl-2-butoxy-8-hydroxy adenine, called SA-2) to affect IL-17 response. The SA-2 activity on the expression of IL-17A and IL-17–related molecules was evaluated in acute and chronic models of asthma as well as in in vivo and in vitro a-galactosyl ceramide (a-GalCer)-driven systems. SA-2 prepriming reduced neutrophils in bronchoalveolar lavage fluid and decreased methacoline-induced airway hyperresponsiveness in murine asthma models. These results were associated with the reduction of IL-17A (and type 2 cytokines) as well as of molecules favoring Th17 (and Th2) development in lung tissue. The IL-17A production in response to a-GalCer by spleen mononuclear cells was inhibited in vitro by the presence of SA-2. Reduced IL-17A (as well as IFN-g and IL-13) serum levels in mice treated with a-GalCer plus SA-2 were also observed. The in vitro results indicated that IL-10 produced by B cells and IL-10–promoting molecules such as IFN-a and IL- 27 by dendritic cells are the major player for SA-2–driven IL-17A (and also IFN-g and IL-13) inhibition. The in vivo experiments with anti-cytokine receptor Abs provided evidence of an early IL-17A inhibition essentially due to IL-10 produced by resident peritoneal cells and of a delayed IL-17A inhibition sustained by IFN-a and IL-27, which in turn drive effector T cells to IL-10 production.
    [Show full text]
  • Interleukin-1And Interleukin-6 Gene Polymorphisms and the Risk of Breast Cancer in Caucasian Women
    Human Cancer Biology Interleukin-1 and Interleukin-6 Gene Polymorphisms and the Risk of Breast Cancer in Caucasian Women Lukas A. Hefler,1, 3 Christoph Grimm,1Tilmann Lantzsch,4 Dieter Lampe,4 Sepp Leodolter,1, 3 Heinz Koelbl,5 Georg Heinze,2 Alexander Reinthaller,1Dan Tong-Cacsire,1Clemens Tempfer,1, 3 and Robert Zeillinger1, 3 Abstract Purpose: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1)andIL-6(IL6) also influence breast cancer risk is unknown. Experimental Design: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [À889 C/T polymorphism of the IL1agene (IL1A), À511C/T polymorphism of the IL1b promoter (IL1B promoter), a polymorphism of IL1b exon 5 (IL1B exon 5 )], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the À174 G/C polymorphism of the IL6 gene (IL6 ) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing. Results: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively.
    [Show full text]
  • IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells
    cells Article IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells Fridolin Franke 1,2, Greg A. Kirchenbaum 1 , Stefanie Kuerten 2 and Paul V. Lehmann 1,* 1 Research & Development Department, Cellular Technology Limited, Shaker Heights, OH 44122, USA; [email protected] (F.F.); [email protected] (G.A.K.) 2 Institute of Anatomy and Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; [email protected] * Correspondence: [email protected]; Tel.: +1-216-965-6311 Received: 3 December 2019; Accepted: 12 February 2020; Published: 13 February 2020 Abstract: Detection of antigen-specific memory B cells for immune monitoring requires their activation, and is commonly accomplished through stimulation with the TLR7/8 agonist R848 and IL-2. To this end, we evaluated whether addition of IL-21 would further enhance this TLR-driven stimulation approach; which it did not. More importantly, as most antigen-specific B cell responses are T cell-driven, we sought to devise a polyclonal B cell stimulation protocol that closely mimics T cell help. Herein, we report that the combination of agonistic anti-CD40, IL-4 and IL-21 affords polyclonal B cell stimulation that was comparable to R848 and IL-2 for detection of influenza-specific memory B cells. An additional advantage of anti-CD40, IL-4 and IL-21 stimulation is the selective activation of IgM+ memory B cells, as well as the elicitation of IgE+ ASC, which the former fails to do. Thereby, we introduce a protocol that mimics physiological B cell activation through helper T cells, including induction of all Ig classes, for immune monitoring of antigen-specific B cell memory.
    [Show full text]
  • Is Interleukin 6 an Early Marker of Injury Severity Following Major Trauma in Humans?
    ORIGINAL ARTICLE Is Interleukin 6 an Early Marker of Injury Severity Following Major Trauma in Humans? Florian Gebhard, MD; Helga Pfetsch, MSc; Gerald Steinbach, MD; Wolf Strecker, MD; Lothar Kinzl, MD; Uwe B. Bru¨ckner, MD Hypothesis: Interleukin 6 (IL-6), a multifunctional cy- of trauma and to relate these results to IL-6 release. tokine, is expressed by various cells after many stimuli and underlies complex regulatory control mechanisms. Results: As early as immediately after trauma, elevated IL-6 Following major trauma, IL-6 release correlates with in- plasma levels occurred. This phenomenon was pronounced jury severity, complications, and mortality. The IL-6 re- in patients with major trauma (ISS, .32). Patients with mi- sponse to injury is supposed to be uniquely consistent nor injury had elevated concentrations as well but to a far and related to injury severity. Therefore, we designed a lesser extent. In surviving patients, IL-6 release correlated prospective study starting as early as at the scene of the with the ISS values best during the first 6 hours after hos- unintentional injury to determine the trauma-related re- pital admission. All patients revealed increased C-reactive lease of plasma IL-6 in multiple injured patients. protein levels within 12 hours following trauma, reflecting the individual injury severity. This was most pronounced Patients and Methods: On approval of the local eth- in patients with the most severe (ISS, .32) trauma. ics committee, 94 patients were enrolled with different injuries following trauma (Injury Severity Score [ISS] me- Conclusions: To our knowledge, this is the first study that dian, 19; range, 3-75).
    [Show full text]
  • Promoter Polymorphism in the Interleukin-10 Confers an Increased
    Research Article Clinics in Oncology Published: 09 Jan, 2019 Promoter Polymorphism in the Interleukin-10 Confers an Increased Risk of DLBCL in Chinese Bao Song1*, Yuhong Liu2, Chuanxi Wang3 and Jie Liu4 1Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital & Institute, Shandong Academy of Medical Sciences, China 2Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, China 3Department of Oncology, Shandong Provincial Hospital, China 4Department of Oncology, Shandong Cancer Hospital & Institute, Shandong Academy of Medical Sciences, China Abstract Findings suggest that genetic polymorphisms in cytokine genes are associated with an increased risk of Non-Hodgkin Lymphoma (NHL) in Caucasians. This study was designed to assess whether single nucleotide polymorphisms in IL-10 promoter play a role in predisposing individuals to NHL in Chinese populations. We genotyped four SNPs in the distal and proximal IL-10 promoter (IL- 10 -3575T/A, IL-10 -1082A/G,-819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis. We conducted this study in 512 NHL cases and 500 age- and sex-matched healthy controls. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and two well-defined subtypes [Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL)]. No significant correlation of IL-10-3575T/A, IL-10-1082A/G,-819T/C and -592A/C polymorphisms to risk of NHL overall. When analyses by subtype, the -1082 AG genotypes and G alleles were associated with a significantly increased risk of DLBCL as compared with the -1082 AA genotype and A alleles (OR=1.64, 95% CI 1.06~2.54, P=0.025 for AG; OR=1.57, 95% CI 1.06-2.31, P=0.023 for G allele).
    [Show full text]
  • Toxicity and Inflammatory Response of Melamine Cyanurate
    Journal of Hong Kong Institute of Medical Laboratory Sciences 2017-2018 Volume 15 No 1 & 2 Lessons Learnt from the Melamine Incident of Paediatric Stones: Toxicity and Inflammatory Response of Melamine Cyanurate Mayur Danny I. Gohel1, John Wai-Man Yuen2, Kam-Lun Hon3, Chi-Fai Ng4 1School of Medical & Health Sciences, Tung Wah College, Homantin, Kowloon, Hong Kong – SAR CHINA. 2School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong –SAR CHINA. 3Department of Paediatrics and 4Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong – SAR CHINA. #Corresponding author: Prof. Mayur Danny I. Gohel, School of Medical & Health Sciences, Tung Wah College, Homantin, Kowloon, Hong Kong. Phone: (852) 3190 6680. E-mail: [email protected] ABSTRACT News regarding drinking milk products contaminated with melamine had gained considerable coverage. The most affected victims had been infants and children with kidney being the most affected organ. There were challenges in detecting and diagnosing renal stones in infants. Paediatric stone disease differs considerably in many aspects from that in adults, with a prevalence of 0.5 cases per 1000 (compared to 70 per 1000 in adults). We attempted to investigate the early cellular events of kidney cells in response to melamine and related lithogenic ions. A two-compartment transwell culture with human kidney cortical WT 9-12 cell line allowed us to investigate the melamine crystals interacting with the apical surface. In response to the clinically relevant ratio of melamine and cyanurate, i.e. 99:1 (v/v), 25% of the cells were destroyed to demonstrate significant disturbance to the tight junction monolayer of cortical epithelium.
    [Show full text]
  • Abstract Background: Tuberculosis (TB) Is a Deadly Transmissible Disease That Can Infect Almost Any Body-Part of the Host but Is Mostly Infect the Lungs
    bioRxiv preprint doi: https://doi.org/10.1101/414110; this version posted September 14, 2018. The copyright holder for this preprint (which was Stagenot certified specific by peer classification review) is the author/funder. of DEGs All rights via reserved. statistical No reuse profiling allowed without and permission. network analysis reveals potential biomarker associated with various stages of TB Aftab Alam1. Nikhat Imam2, Mohd Murshad Ahmed1, Safiya Tazyeen1, Anam Farooqui1, Shahnawaz Ali1, Md. Zubbair Malik1 and Romana Ishrat*1 1Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi-110025 (India) 2Institute of Computer Science & Information Technology, Department of Mathematics, Magadh University, Bodh Gaya-824234 (Bihar, India) Abstract Background: Tuberculosis (TB) is a deadly transmissible disease that can infect almost any body-part of the host but is mostly infect the lungs. It is one of the top 10 causes of death worldwide. In the 30 high TB burden countries, 87% of new TB cases occurred in 2016. Seven countries: India, Indonesia, China, Philippines, Pakistan, Nigeria, and South Africa accounted for 64% of the new TB cases. To stop the infection and progression of the disease, early detection of TB is important. In our study, we used microarray data set and compared the gene expression profiles obtained from blood samples of patients with different datasets of Healthy control, Latent infection, Active TB and performed network-based analysis of DEGs to identify potential biomarker. We want to observe the transition of genes from normal condition to different stages of the TB and identify, annotate those genes/pathways/processes that play key role in the progression of TB disease during its cyclic interventions in human body.
    [Show full text]