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.
abstract: 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.
authors: Brain Infections Group, Department of Clinical Infection, Microbiology and Immunology,  Institute of Infection and Global Health, University of Liverpool,  United Kingdom.
authors: Michael J
authors: MJ
authors: Griffiths
authors: Mong H
authors: MH
authors: Ooi
authors: See C
authors: SC
authors: Wong
authors: Anand
authors: A
authors: Mohan
authors: Yuwana
authors: Y
authors: Podin
authors: David
authors: D
authors: Perera
authors: Chae H
authors: CH
authors: Chieng
authors: Phaik H
authors: PH
authors: Tio
authors: Mary J
authors: MJ
authors: Cardosa
authors: Tom
authors: T
authors: Solomon
mesh_terms: D015415:Biomarkers; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000209:etiology*; D029821:Enterovirus A, Human; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000378:metabolism; D006232:Hand, Foot and Mouth Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood*; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D011379:Prognosis; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D016179:Granulocyte Colony-Stimulating Factor