title: Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.
abstract: BACKGROUND
  Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.
  
  
  METHODS
  We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.
  
  
  RESULTS
  Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).
  
  
  CONCLUSIONS
  Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.
authors.affiliation: The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.|The Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Benedict D
authors.initials: BD
authors.lastname: Michael
authors.affiliation: The Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom.|Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Griffiths
authors.affiliation: Public Health England, London, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Granerod
authors.affiliation: Public Health England, London, United Kingdom.|Influenza and measles laboratory, IOC, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: Chelsea and Westminster NHS Foundation Trust, London, United Kingdom.
authors.forename: Nicholas W S
authors.initials: NW
authors.lastname: Davies
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester, United Kingdom.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.|The Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Solomon
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000097:blood / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000134:cerebrospinal fluid / Q000145:classification; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D003937:Diagnosis, Differential; D004660:Encephalitis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000276:immunology; D018792:Encephalitis, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D000069544:Infectious Encephalitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D007958:Leukocyte Count; D008297:Male; D015337:Multicenter Studies as Topic; D009181:Mycoses / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D020361:Paraneoplastic Syndromes, Nervous System / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D009195:Peroxidase / Q000097:blood / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D016781:Toxoplasmosis, Cerebral / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D009195:Peroxidase