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: Benedict D Michael, Michael J Griffiths, Julia Granerod, David Brown, Nicholas W S Davies, Ray Borrow, Tom Solomon
• Journal: PloS one (PLoS One) Vol. 11 Issue 1 Pg. e0146288 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 26808276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cell Adhesion Molecules
• Chemokines
• Cytokines
• Peroxidase

Topics

• Adult
• Bacterial Infections (blood, cerebrospinal fluid)
• Biomarkers
• Cell Adhesion Molecules (blood, cerebrospinal fluid)
• Chemokines (cerebrospinal fluid, classification)
• Cytokines (blood, cerebrospinal fluid)
• Diagnosis, Differential
• Encephalitis (blood, cerebrospinal fluid, etiology, immunology)
• Encephalitis, Viral (blood, cerebrospinal fluid, diagnosis)
• England (epidemiology)
• Female
• Humans
• Infectious Encephalitis (blood, cerebrospinal fluid, diagnosis)
• Leukocyte Count
• Male
• Multicenter Studies as Topic
• Mycoses (blood, cerebrospinal fluid, diagnosis)
• Paraneoplastic Syndromes, Nervous System (blood, cerebrospinal fluid, diagnosis)
• Peroxidase (blood, cerebrospinal fluid)
• Retrospective Studies
• Toxoplasmosis, Cerebral (blood, cerebrospinal fluid, diagnosis)