In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis

Background. Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood. Methods. We measured levels of 30 chemokines and cytokines in serum and cerebrospi...

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Main Authors: Griffiths, Michael J., Ooi, Mong H., Wong, See Chang, Mohan, Anand, Podin, Yuwana, Perera, David, Chieng, Chae H., Tio, Phaik Hooi, Cardosa, Mary Jane, Solomon, Tom
Format: Article
Language:English
Published: Oxford Journals 2012
Subjects:
Online Access:http://ir.unimas.my/id/eprint/6695/
http://ir.unimas.my/id/eprint/6695/1/In%20Enterovirus%2071%20Encephalitis%20With%20Cardio-respiratory%20%28abstract%29.pdf
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author Griffiths, Michael J.
Ooi, Mong H.
Wong, See Chang
Mohan, Anand
Podin, Yuwana
Perera, David
Chieng, Chae H.
Tio, Phaik Hooi
Cardosa, Mary Jane
Solomon, Tom
author_facet Griffiths, Michael J.
Ooi, Mong H.
Wong, See Chang
Mohan, Anand
Podin, Yuwana
Perera, David
Chieng, Chae H.
Tio, Phaik Hooi
Cardosa, Mary Jane
Solomon, Tom
author_sort Griffiths, Michael J.
building UNIMAS Institutional Repository
collection Online Access
description Background. Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood. Methods. We measured levels of 30 chemokines and cytokines in serum and cerebrospinal fluid (CSF) samples from Malaysian children hospitalized with EV71 infection (n = 88), comprising uncomplicated HFMD (n = 47), meningitis (n = 8), acute flaccid paralysis (n = 1), encephalitis (n = 21), and encephalitis with cardiorespiratory compromise (n = 11). Four of the latter patients died. Results. Both pro-inflammatory and anti-inflammatory mediator levels were elevated, with different patterns of mediator abundance in the CSF and vascular compartments. Serum concentrations of interleukin 1β (IL-1β), interleukin 1 receptor antagonist (IL-1Ra), and granulocyte colony-stimulating factor (G-CSF) were raised significantly in patients who developed cardio-respiratory compromise (P = .013, P = .004, and P < .001, respectively). Serum IL-1Ra and G-CSF levels were also significantly elevated in patients who died, with a serum G-CSF to interleukin 5 ratio of >100 at admission being the most accurate prognostic marker for death (P < .001; accuracy, 85.5%; sensitivity, 100%; specificity, 84.7%). Conclusions. Given that IL-1β has a negative inotropic action on the heart, and that both its natural antagonist, IL-1Ra, and G-CSF are being assessed as treatments for acute cardiac impairment, the findings suggest we have identified functional markers of EV71-related cardiac dysfunction and potential treatment options.
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spelling unimas-66952015-04-07T07:40:45Z http://ir.unimas.my/id/eprint/6695/ In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis Griffiths, Michael J. Ooi, Mong H. Wong, See Chang Mohan, Anand Podin, Yuwana Perera, David Chieng, Chae H. Tio, Phaik Hooi Cardosa, Mary Jane Solomon, Tom Q Science (General) QR180 Immunology QR355 Virology R Medicine (General) Background. Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood. Methods. We measured levels of 30 chemokines and cytokines in serum and cerebrospinal fluid (CSF) samples from Malaysian children hospitalized with EV71 infection (n = 88), comprising uncomplicated HFMD (n = 47), meningitis (n = 8), acute flaccid paralysis (n = 1), encephalitis (n = 21), and encephalitis with cardiorespiratory compromise (n = 11). Four of the latter patients died. Results. Both pro-inflammatory and anti-inflammatory mediator levels were elevated, with different patterns of mediator abundance in the CSF and vascular compartments. Serum concentrations of interleukin 1β (IL-1β), interleukin 1 receptor antagonist (IL-1Ra), and granulocyte colony-stimulating factor (G-CSF) were raised significantly in patients who developed cardio-respiratory compromise (P = .013, P = .004, and P < .001, respectively). Serum IL-1Ra and G-CSF levels were also significantly elevated in patients who died, with a serum G-CSF to interleukin 5 ratio of >100 at admission being the most accurate prognostic marker for death (P < .001; accuracy, 85.5%; sensitivity, 100%; specificity, 84.7%). Conclusions. Given that IL-1β has a negative inotropic action on the heart, and that both its natural antagonist, IL-1Ra, and G-CSF are being assessed as treatments for acute cardiac impairment, the findings suggest we have identified functional markers of EV71-related cardiac dysfunction and potential treatment options. Oxford Journals 2012-07-24 Article PeerReviewed text en http://ir.unimas.my/id/eprint/6695/1/In%20Enterovirus%2071%20Encephalitis%20With%20Cardio-respiratory%20%28abstract%29.pdf Griffiths, Michael J. and Ooi, Mong H. and Wong, See Chang and Mohan, Anand and Podin, Yuwana and Perera, David and Chieng, Chae H. and Tio, Phaik Hooi and Cardosa, Mary Jane and Solomon, Tom (2012) In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis. Journal Of Infectious Diseases, 211 (8). ISSN 1537-6613 http://jid.oxfordjournals.org/content/206/6/881.long
spellingShingle Q Science (General)
QR180 Immunology
QR355 Virology
R Medicine (General)
Griffiths, Michael J.
Ooi, Mong H.
Wong, See Chang
Mohan, Anand
Podin, Yuwana
Perera, David
Chieng, Chae H.
Tio, Phaik Hooi
Cardosa, Mary Jane
Solomon, Tom
In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis
title In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis
title_full In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis
title_fullStr In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis
title_full_unstemmed In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis
title_short In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1β, Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis
title_sort in enterovirus 71 encephalitis with cardio-respiratory compromise, elevated interleukin 1β, interleukin 1 receptor antagonist, and granulocyte colony-stimulating factor levels are markers of poor prognosis
topic Q Science (General)
QR180 Immunology
QR355 Virology
R Medicine (General)
url http://ir.unimas.my/id/eprint/6695/
http://ir.unimas.my/id/eprint/6695/
http://ir.unimas.my/id/eprint/6695/1/In%20Enterovirus%2071%20Encephalitis%20With%20Cardio-respiratory%20%28abstract%29.pdf