Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.
Journal
The Pediatric infectious disease journal
ISSN: 1532-0987
Titre abrégé: Pediatr Infect Dis J
Pays: United States
ID NLM: 8701858
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
medline:
16
8
2023
pubmed:
18
7
2023
entrez:
18
7
2023
Statut:
ppublish
Résumé
Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.
Sections du résumé
BACKGROUND
Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies.
METHODS
We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease.
RESULTS
During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate.
CONCLUSIONS
Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.
Identifiants
pubmed: 37463399
doi: 10.1097/INF.0000000000003990
pii: 00006454-202309000-00013
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Cytokines
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
792-800Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Supported by Ministerio de Ciencia Tecnología e Innovación, grant 112451929026 (D.M.S.) and the Sistema General de Regalías del Departamento del Huila (S.G.R.), project BPIN 2020000100145 (C.F.N.) and Vicerrectoría de Investigación y Proyección Social, Universidad Surcolombiana (C.F.N.). The other authors have no conflicts of interest to disclose.
Références
Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature. 2013;496:504–507.
Yang X, Quam MBM, Zhang T, et al. Global burden for dengue and the evolving pattern in the past 30 years. J Travel Med. 2021;28:taab146.
Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. In: Geneva; 2009. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23762963 .
Tomashek KM, Gregory CJ, Rivera Sánchez A, et al. Dengue deaths in Puerto Rico: lessons learned from the 2007 epidemic. PLoS NeglTrop Dis. 2012;6:e1614e1614.
Carabali M, Hernandez LM, Arauz MJ, et al. Why are people with dengue dying? A scoping review of determinants for dengue mortality. BMC Infect Dis. 2015;15:301.
Ranjit S, Kissoon N, Gandhi D, et al. Early differentiation between dengue and septic shock by comparison of admission hemodynamic, clinical, and laboratory variables: a pilot study. Pediatr Emerg Care. 2007;23:368–375.
Wentowski C, Ingles DP, Nielsen ND. Sepsis 2021: a review. Anaesth Crit Care Pain Med. 2021;22:676–684.
Lee YH, Leong W-Y, Wilder-Smith A. Markers of dengue severity: a systematic review of cytokines and chemokines. J Gen Virol. 2016;97:3103–3119.
Rothman AL. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol. 2011;11:532–543.
Libraty DH, Endy TP, Houng H-SH, et al. Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections. J Infect Dis. 2002;185:1213–1221.
Butthep P, Chunhakan S, Yoksan S, et al. Alteration of cytokines and chemokines during febrile episodes associated with endothelial cell damage and plasma leakage in dengue hemorrhagic fever. Pediatr Infect Dis J. 2012;31:e232–e238.
Gårdlund B, Sjölin J, Nilsson A, et al. Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. J Infect Dis. 1995;172:296–301.
Bozza FA, Salluh JI, Japiassu AM, et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care. 2007;11:R49.
Innis BL, Nisalak A, Nimmannitya S, et al. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg. 1989;40:418–427.
Perdomo-Celis F, Salgado DM, Castañeda DM, et al. Viability and functionality of cryopreserved peripheral blood mononuclear cells in pediatric dengue. Clin Vaccine Immunol. 2016;23:417–426.
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2–8.
Watson RS, Carcillo JA, Linde-Zwirble WT, et al. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003;167:695–701.
Hartman ME, Linde-Zwirble WT, Angus DC, et al. Trends in the epidemiology of pediatric severe sepsis*. Pediatr Crit Care Med. 2013;14:686–693.
Guerrero CD, Arrieta AF, Ramirez ND, et al. High plasma levels of soluble ST2 but not its ligand IL-33 is associated with severe forms of pediatric dengue. Cytokine. 2013;61:766–771.
Lee I-K, Liu J-W, Yang KD. Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. Am J Trop Med Hyg. 2005;72:221–226.
Thein T-L, Ng E-L, Yeang MS, et al. Risk factors for concurrent bacteremia in adult patients with dengue. J Microbiol Immunol Infect. 2017;50:314–320.
John AL, Rathore APS. Adaptive immune responses to primary and secondary dengue virus infections. Nat Rev Immunol. 2019;19:218–230.
Rathakrishnan A, Wang SM, Hu Y, et al. Cytokine Expression Profile of Dengue Patients at Different Phases of Illness. PLoS One. 2012;7:e52215.
Arias J, Valero N, Mosquera J, et al. Increased expression of cytokines, soluble cytokine receptors, soluble apoptosis ligand and apoptosis in dengue. Virology. 2014;452–453:42–51.
Huang J, Liang W, Chen S, et al. Serum cytokine profiles in patients with dengue fever at the acute infection phase. Dis Markers. 2018;2018:8403937.
van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17:407–420.
Hober D, Poli L, Roblin B, et al. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in dengue-infected patients. Am J Trop Med Hyg. 1993;48:324–331.
Sullivan JS, Kilpatrick L, Costarino AT Jr, et al. Correlation of plasma cytokine elevations with mortality rate in children with sepsis. J Pediatr. 1992;120:510–515.
Angurana SK, Bansal A, Muralidharan J, et al. Cytokine levels in critically Ill children with severe sepsis and their relation with the severity of illness and mortality. J Intensive Care Med. 2021;36:576–583.
Hazelzet JA, van der Voort E, Lindemans J, et al. Relation between cytokines and routine laboratory data in children with septic shock and purpura. Intensive Care Med. 1994;20:371–374.
Juffrie M, van Der Meer GM, Hack CE, et al. Inflammatory mediators in dengue virus infection in children: interleukin-8 and its relationship to neutrophil degranulation. Infect Immun. 2000;68:702–707.
Harada A, Sekido N, Akahoshi T, et al. Essential involvement of interleukin-8 (IL-8) in acute inflammation. J Leukoc Biol. 1994;56:559–564.
Kurane I, Innis BL, Nimmannitya S, et al. Activation of T lymphocytes in dengue virus infections. high levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue. J Clin Invest. 1991;88:1473–1480.
Spear ML, Stefano JL, Fawcett P, et al. Soluble interleukin-2 receptor as a predictor of neonatal sepsis. J Pediatr. 1995;126:982–985.
Damoiseaux J. The IL-2 – IL-2 receptor pathway in health and disease: the role of the soluble IL-2 receptor. Clin Immunol. 2020;218:108515.
Valero N, Larreal Y, Espina LM, et al. Elevated levels of interleukin-2 receptor and intercellular adhesion molecule 1 in sera from a Venezuelan cohort of patients with dengue. Arch Virol. 2008;153:199–203.
Çekmez F, Fidanci MK, Ayar G, et al. Diagnostic value of Upar, IL-33, and ST2 levels in childhood sepsis. Clin Lab. 2016;62:751–755.
Bandara G, Beaven MA, Olivera A, et al. Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33. Eur J Immunol. 2015;45:3034–3044.
St John AL, Rathore APS, Raghavan B, et al. Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife. 2013;2:e00481.
Houghton-Triviño N, Salgado DM, Rodríguez JA, et al. Levels of soluble ST2 in serum associated with severity of dengue due to tumour necrosis factor alpha stimulation. J Gen Virol. 2010;91:697–706.
Rathore AP, Mantri CK, Aman SA, et al. Dengue virus-elicited tryptase induces endothelial permeability and shock. J Clin Invest. 2019;129:4180–4193.
Rathore APS, Senanayake M, Athapathu AS, et al. Serum chymase levels correlate with severe dengue warning signs and clinical fluid accumulation in hospitalized pediatric patients. Sci Rep. 2020;10:11856.
Mildner M, Storka A, Lichtenauer M, et al. Primary sources and immunological prerequisites for sST2 secretion in humans. Cardiovasc Res. 2010;87:769–777.
Griesenauer B, Paczesny S. The ST2/IL-33 axis in immune cells during inflammatory diseases. Front Immunol. 2017;8:475.
Alves-Filho JC, Sônego F, Souto FO, et al. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010;16:708–712.
Perdomo-Celis F, Romero F, Salgado DM, et al. Identification and characterization at the single-cell level of cytokine-producing circulating cells in children with dengue. J Infect Dis. 2018;217:1472–1480.
Kwissa M, Nakaya HI, Onlamoon N, et al. Dengue virus infection induces expansion of a CD14 + CD16 + monocyte population that stimulates plasmablast differentiation. Cell Host Microbe. 2014;16:115–127.
Toro JF, Salgado DM, Vega R, et al. Total and envelope protein-specific antibody-secreting cell response in pediatric dengue is highly modulated by age and subsequent infections. PLoS One. 2016;11:e0161795.
Chareonsirisuthigul T, Kalayanarooj S, Ubol S. Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells. J Gen Virol. 2007;88:365–375.
Boonnak K, Dambach KM, Donofrio GC, et al. Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection. J Virol. 2011;85:1671–1683.
Latifi SQ, O’Riordan MA, Levine AD. Interleukin-10 controls the onset of irreversible septic shock. Infect Immun. 2002;70:4441–4446.
Anon S, Chuanpis A, Endy TP, et al. Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic fever. J Virol. 2007;81:1592–1600.
Furuta T, Murao LA, Lan NTP, et al. Association of mast cell-derived VEGF and proteases in dengue shock syndrome. PLoS NeglTrop Dis. 2012;6:e1505.
Simons M, Gordon E, Claesson-Welsh L. Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol. 2016;17:611–625.
Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell. 2019;176:1248–1264.
Vianna RCS, Gomes RN, Bozza FA, et al. Antibiotic treatment in a murine model of sepsis: impact on cytokines and endotoxin release. Shock. 2004;21:115–120.
Restrepo BN, Ramirez RE, Arboleda M, et al. Serum levels of cytokines in two ethnic groups with dengue virus infection. Am J Trop Med Hyg. 2008;79:673–677.