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Published in: Journal of Clinical Immunology 5/2009

01-09-2009

Sequential Changes in Serum Cytokines Reflect Viral RNA Kinetics in Target Organs of a Coxsackievirus B Infection in Mice

Authors: Magnus Lundgren, Per Ola Darnerud, Jonas Blomberg, Göran Friman, Nils-Gunnar Ilbäck

Published in: Journal of Clinical Immunology | Issue 5/2009

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Abstract

Introduction

The pattern of cytokine responses related to viral replication during the course of the common human coxsackievirus B3 (CVB3) infection is not known.

Methods

Serum levels of 21 cytokines and chemokines were studied (Luminex technique) in CVB3-infected in mice on days 3, 6, and 9 post-infection (p.i.). CVB3 was measured quantitatively (reverse transcriptase polymerase chain reaction) in the liver and pancreas.

Results

Virus levels peaked on day 3 in both the liver and pancreas, but were 1,000-fold higher in the pancreas. IL-17α, IFN-γ, KC, MCP-1, MIP1β, and RANTES were detected on all days. On day 3 p.i., IL-6, IL-12(p40), KC, MCP-1, RANTES, and TNF-α were found to peak. On day 6 p.i., IL-1β, IL-9, IL-12(p70), IL-13, IL-17α, and IFN-γ peaked. On day 9 p.i., MIP1β, IL-1β, MCP-1, and TNF-α were still increased. These changes in cytokines may be used to monitor the progress of enteroviral infections in clinical settings.
Literature
4.
go back to reference Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MA. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill Summ. 2006;55:1–20.PubMed Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MA. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill Summ. 2006;55:1–20.PubMed
5.
go back to reference Grist NR, Reid D. Epidemiology of viral infections in the heart. In: Banatvala JE, editor. Viral Infections of the heart. London: Edward Arnold; 1993. p. 23–31. Grist NR, Reid D. Epidemiology of viral infections in the heart. In: Banatvala JE, editor. Viral Infections of the heart. London: Edward Arnold; 1993. p. 23–31.
6.
go back to reference Moya-Suri V, Schlosser M, Zimmermann K, Rjasanowski I, Gurtler L, Mentel R. Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies. J Med Microbiol. 2005;54:879–83. doi:10.1099/jmm.0.46015-0.PubMedCrossRef Moya-Suri V, Schlosser M, Zimmermann K, Rjasanowski I, Gurtler L, Mentel R. Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies. J Med Microbiol. 2005;54:879–83. doi:10.​1099/​jmm.​0.​46015-0.PubMedCrossRef
8.
go back to reference Woodruff JF. Viral myocarditis. A review. Am J Pathol. 1980;101:425–84.PubMed Woodruff JF. Viral myocarditis. A review. Am J Pathol. 1980;101:425–84.PubMed
10.
go back to reference Beisel WR. Metabolic response of the host to infections. In: Feigin RD, Cherry JD, editors. Textbook of pediatric infectious disease. Philadelphia: Saunders; 1998. p. 54–69. Beisel WR. Metabolic response of the host to infections. In: Feigin RD, Cherry JD, editors. Textbook of pediatric infectious disease. Philadelphia: Saunders; 1998. p. 54–69.
11.
go back to reference Fairweather D, Rose NR. Women and autoimmune diseases. Emerg Infect Dis. 2004;10:2005–11.PubMed Fairweather D, Rose NR. Women and autoimmune diseases. Emerg Infect Dis. 2004;10:2005–11.PubMed
13.
go back to reference Ilback NG, Fohlman J, Slorach S, Friman G. Effects of the immunomodulator LS 2616 on lymphocyte subpopulations in murine coxsackievirus B3 myocarditis. J Immunol. 1989;142:3225–8.PubMed Ilback NG, Fohlman J, Slorach S, Friman G. Effects of the immunomodulator LS 2616 on lymphocyte subpopulations in murine coxsackievirus B3 myocarditis. J Immunol. 1989;142:3225–8.PubMed
14.
go back to reference Ilback NG, Wesslen L, Pauksen K, Stalhandske T, Friman G, Fohlman J. Effects of the antiviral WIN 54954 and the immune modulator LS 2616 on cachectin/TNF and gamma-interferon responses during viral heart disease. Scand J Infect Dis Suppl. 1993;88:117–23.PubMed Ilback NG, Wesslen L, Pauksen K, Stalhandske T, Friman G, Fohlman J. Effects of the antiviral WIN 54954 and the immune modulator LS 2616 on cachectin/TNF and gamma-interferon responses during viral heart disease. Scand J Infect Dis Suppl. 1993;88:117–23.PubMed
15.
go back to reference Curfs JH, Meis JF, Hoogkamp-Korstanje JA. A primer on cytokines: sources, receptors, effects, and inducers. Clin Microbiol Rev. 1997;10:742–80.PubMed Curfs JH, Meis JF, Hoogkamp-Korstanje JA. A primer on cytokines: sources, receptors, effects, and inducers. Clin Microbiol Rev. 1997;10:742–80.PubMed
17.
go back to reference Fairweather D, Frisancho-Kiss S, Gatewood S, Njoku D, Steele R, Barrett M, et al. Mast cells and innate cytokines are associated with susceptibility to autoimmune heart disease following coxsackievirus B3 infection. Autoimmunity. 2004;37:131–45. doi:10.1080/0891693042000196200.PubMedCrossRef Fairweather D, Frisancho-Kiss S, Gatewood S, Njoku D, Steele R, Barrett M, et al. Mast cells and innate cytokines are associated with susceptibility to autoimmune heart disease following coxsackievirus B3 infection. Autoimmunity. 2004;37:131–45. doi:10.​1080/​0891693042000196​200.PubMedCrossRef
21.
go back to reference Ilback NG, Mohammed A, Fohlman J, Friman G. Cardiovascular lipid accumulation with Coxsackie B virus infection in mice. Am J Pathol. 1990;136:159–67.PubMed Ilback NG, Mohammed A, Fohlman J, Friman G. Cardiovascular lipid accumulation with Coxsackie B virus infection in mice. Am J Pathol. 1990;136:159–67.PubMed
25.
go back to reference Lammi N, Karvonen M, Tuomilehto J. Do microbes have a causal role in type 1 diabetes? Med Sci Monit. 2005;11:RA63–9.PubMed Lammi N, Karvonen M, Tuomilehto J. Do microbes have a causal role in type 1 diabetes? Med Sci Monit. 2005;11:RA63–9.PubMed
26.
27.
go back to reference Stechova K, Bohmova K, Vrabelova Z, Sepa A, Stadlerova G, Zacharovova K, et al. High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes. Diabetes Metab Res Rev. 2007;23:462–71. doi:10.1002/dmrr.718.PubMedCrossRef Stechova K, Bohmova K, Vrabelova Z, Sepa A, Stadlerova G, Zacharovova K, et al. High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes. Diabetes Metab Res Rev. 2007;23:462–71. doi:10.​1002/​dmrr.​718.PubMedCrossRef
31.
go back to reference Fairweather D, Yusung S, Frisancho S, Barrett M, Gatewood S, Steele R, et al. IL-12 receptor beta 1 and Toll-like receptor 4 increase IL-1 beta- and IL-18-associated myocarditis and coxsackievirus replication. J Immunol. 2003;170:4731–7.PubMed Fairweather D, Yusung S, Frisancho S, Barrett M, Gatewood S, Steele R, et al. IL-12 receptor beta 1 and Toll-like receptor 4 increase IL-1 beta- and IL-18-associated myocarditis and coxsackievirus replication. J Immunol. 2003;170:4731–7.PubMed
32.
go back to reference Matsuzaki G, Umemura M. Interleukin-17 as an effector molecule of innate and acquired immunity against infections. Microbiol Immunol. 2007;51:1139–47.PubMed Matsuzaki G, Umemura M. Interleukin-17 as an effector molecule of innate and acquired immunity against infections. Microbiol Immunol. 2007;51:1139–47.PubMed
33.
go back to reference Bozic CR, Gerard NP, von Uexkull-Guldenband C, Kolakowski LF Jr, Conklyn MJ, Breslow R, et al. The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. J Biol Chem. 1994;269:29355–8.PubMed Bozic CR, Gerard NP, von Uexkull-Guldenband C, Kolakowski LF Jr, Conklyn MJ, Breslow R, et al. The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. J Biol Chem. 1994;269:29355–8.PubMed
34.
go back to reference Lee J, Cacalano G, Camerato T, Toy K, Moore MW, Wood WI. Chemokine binding and activities mediated by the mouse IL-8 receptor. J Immunol. 1995;155:2158–64.PubMed Lee J, Cacalano G, Camerato T, Toy K, Moore MW, Wood WI. Chemokine binding and activities mediated by the mouse IL-8 receptor. J Immunol. 1995;155:2158–64.PubMed
36.
go back to reference Kwon D, Fuller AC, Palma JP, Choi IH, Kim BS. Induction of chemokines in human astrocytes by picornavirus infection requires activation of both AP-1 and NF-kappa B. Glia. 2004;45:287–96. doi:10.1002/glia.10331.PubMedCrossRef Kwon D, Fuller AC, Palma JP, Choi IH, Kim BS. Induction of chemokines in human astrocytes by picornavirus infection requires activation of both AP-1 and NF-kappa B. Glia. 2004;45:287–96. doi:10.​1002/​glia.​10331.PubMedCrossRef
37.
go back to reference Martin T, Cardarelli PM, Parry GC, Felts KA, Cobb RR. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1. Eur J Immunol. 1997;27:1091–7. doi:10.1002/eji.1830270508.PubMedCrossRef Martin T, Cardarelli PM, Parry GC, Felts KA, Cobb RR. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1. Eur J Immunol. 1997;27:1091–7. doi:10.​1002/​eji.​1830270508.PubMedCrossRef
38.
go back to reference Mukaida N, Mahe Y, Matsushima K. Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines. J Biol Chem. 1990;265:21128–33.PubMed Mukaida N, Mahe Y, Matsushima K. Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines. J Biol Chem. 1990;265:21128–33.PubMed
42.
go back to reference Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8:223–46.PubMed Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8:223–46.PubMed
46.
go back to reference Zhernakova A, Alizadeh BZ, Eerligh P, Hanifi-Moghaddam P, Schloot NC, Diosdado B, et al. Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes. Genes Immun. 2006;7:544–9. doi:10.1038/sj.gene.6364326.PubMedCrossRef Zhernakova A, Alizadeh BZ, Eerligh P, Hanifi-Moghaddam P, Schloot NC, Diosdado B, et al. Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes. Genes Immun. 2006;7:544–9. doi:10.​1038/​sj.​gene.​6364326.PubMedCrossRef
47.
go back to reference Lohmann T, Laue S, Nietzschmann U, Kapellen TM, Lehmann I, Schroeder S, et al. Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes. Diabetes. 2002;51:2474–80. doi:10.2337/diabetes.51.8.2474.PubMedCrossRef Lohmann T, Laue S, Nietzschmann U, Kapellen TM, Lehmann I, Schroeder S, et al. Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes. Diabetes. 2002;51:2474–80. doi:10.​2337/​diabetes.​51.​8.​2474.PubMedCrossRef
Metadata
Title
Sequential Changes in Serum Cytokines Reflect Viral RNA Kinetics in Target Organs of a Coxsackievirus B Infection in Mice
Authors
Magnus Lundgren
Per Ola Darnerud
Jonas Blomberg
Göran Friman
Nils-Gunnar Ilbäck
Publication date
01-09-2009
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 5/2009
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9294-8

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