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Open Access 01-12-2019 | Multiple Sclerosis | Research

Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases

Authors: Gildas Lepennetier, Zsuzsanna Hracsko, Marina Unger, Martijn Van Griensven, Verena Grummel, Markus Krumbholz, Achim Berthele, Bernhard Hemmer, Markus C. Kowarik

Published in: Journal of Neuroinflammation | Issue 1/2019

Abstract

Background

Cytokines play multiple roles during neuro-inflammatory processes and several cytokines have been studied in the context of specific diseases. This study provides a comprehensive picture of cerebrospinal fluid (CSF) changes during neuro-inflammation by analyzing multiple cytokines in combination with immune cell subsets and standard CSF parameters.

Methods

Using multiplex assays, we simultaneously measured 36 cytokines (CCL1–3, CCL7, CCL8, CCL11, CCL13, CCL19, CCL20, CCL22–27, CXCL1, CXCL2, CXCL5, CXCL6, CXCL8, CXCL9, CXCL11–13, CXCL16, CX3CL1, IL2, IL4, IL6, IL10, IL16, GM-CSF, IFNγ, MIF, TNFα, and MIB1β) in the CSF and serum of 75 subjects. Diagnoses included clinically isolated syndrome and relapsing-remitting multiple sclerosis (MS, n = 18), secondary progressive MS (n = 8), neuro-syphilis (n = 6), Lyme neuro-borreliosis (n = 13), bacterial and viral meningitis (n = 20), and patients with non-inflammatory neurological diseases (NIND, n = 10). Cytokine concentrations were correlated with CSF standard parameters and CSF immune cell subsets (CD4 and CD8 T cells, B cells, plasmablasts, monocytes, and NK cells) quantified by flow cytometry.

Results

We observed increased levels of multiple cytokines (26/36) in patients with neuro-inflammatory diseases when compared to NIND that consistently correlated with CSF cell count and Q_Albumin. Most CSF cytokine concentrations correlated with each other, but correlations between CSF and serum values were scarce (3/36). Within the CSF compartment, CXCL13 showed a strong association with B cells when analyzing all patients, as well as patients with an intact blood-brain barrier (BBB). NK cells positively correlated with CSF concentrations of multiple cytokines (22/36) when analyzing all patients. These correlations were maintained when looking at patients with a disrupted BBB but not detectable in patients with an intact BBB.

Conclusions

Under conditions of neuro-inflammation, multiple CSF cytokines are regulated in parallel and most likely produced locally. A combined increase of CSF CXCL13 levels and B cells occurs under conditions of an intact BBB. Under conditions of a disrupted BBB, CSF NK cells show significantly increased values and seem to have a major contribution to overall inflammatory processes, reflected by a strong correlation with multiple cytokines. Future studies are necessary to address the exact kinetics of these cytokines during neuro-inflammation and their relation to specific diseases phenotypes.

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Title: Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases
Authors: Gildas Lepennetier
Zsuzsanna Hracsko
Marina Unger
Martijn Van Griensven
Verena Grummel
Markus Krumbholz
Achim Berthele
Bernhard Hemmer
Markus C. Kowarik
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Multiple Sclerosis
Syphilis
Meningitis
Cytokines
Published in: Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-019-1601-6

2024 ASCO Annual Meeting

Springer Medicine

Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases

Abstract

Background

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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