Journal Article

Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology

Michael, Benedict D., Griffiths, Michael J., Granerod, Julia, Davies, Nicholas W. S., Brown, David, Borrow, Ray, Solomon, Tom

2016

Overview

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. 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. 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). 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Bacterial Infections - blood / Bacterial Infections - cerebrospinal fluid / Biology and Life Sciences / Biomarkers / Brain / Cell Adhesion Molecules - blood / Cell Adhesion Molecules - cerebrospinal fluid / Cerebrospinal fluid / Chemokines / Chemokines - cerebrospinal fluid / Chemokines - classification / Classification / Cytokines / Cytokines - blood / Cytokines - cerebrospinal fluid / Diagnosis, Differential / Diagnostic tests / Disease / Encephalitis / Encephalitis - blood / Encephalitis - cerebrospinal fluid / Encephalitis - etiology / Encephalitis - immunology / Encephalitis, Viral - blood / Encephalitis, Viral - cerebrospinal fluid / Encephalitis, Viral - diagnosis / England - epidemiology / Etiology / Female / Herpes viruses / Humans / Infections / Infectious diseases / Infectious Encephalitis - blood / Infectious Encephalitis - cerebrospinal fluid / Infectious Encephalitis - diagnosis / Inflammation / Influenza / Leukocyte Count / Leukocytes (neutrophilic) / Male / Measurement methods / Medicine and Health Sciences / Multicenter Studies as Topic / Multivariate analysis / Mycoses - blood / Mycoses - cerebrospinal fluid / Mycoses - diagnosis / Neutrophils / Paraneoplastic Syndromes, Nervous System - blood / Paraneoplastic Syndromes, Nervous System - cerebrospinal fluid / Paraneoplastic Syndromes, Nervous System - diagnosis / Pathogenesis / Patients / People and places / Peroxidase / Peroxidase - blood / Peroxidase - cerebrospinal fluid / Public health / R&D / Research & development / Retrospective Studies / Toxoplasmosis, Cerebral - blood / Toxoplasmosis, Cerebral - cerebrospinal fluid / Toxoplasmosis, Cerebral - diagnosis / Zoonoses