Cerebrospinal Fluid Interleukin-6 in Central Nervous System Inflammatory Diseases

Wullschleger et al. published a paper in 2013 about the role of interleukin-6 (IL-6) as a potential biomarker (https://en.wikipedia.org/wiki/Biomarker) of central nervous system (CNS) diseases. Being able to differentiate between diseases like multiple sclerosis (MS) and other inflammatory neurological diseases, like Transverse Myelitis (TM), is extremely important for a clinician to be able to do, as the treatments and disease course are different for these diseases.  It is also important because it is unlikely that there will ever be a single biomarker that can be used to diagnose MS, but there may be several biomarkers, like IL-6, that can differentiate MS from other diseases.

Cerebrospinal fluid (CSF) is thought to be one place where biomarkers related to chronic CNS diseases such as MS might be found.  Wullschleger et al. compared IL-6 levels in CSF samples of 374 individuals in several disease categories.  They tested 117 CSF samples of those with demyelinating diseases, including 76 with MS, and 30 with optic neuritis (ON).  They also tested the CSF of 10 people with idiopathic transverse myelitis (TM),35 CSF samples from people with other inflammatory neurological diseases (e.g., neurolupus), and 212 samples with non-inflammatory neurological diseases (e.g., normal pressure hydrocephalus).

IL-6 is a pleiotropic glycoprotein cytokine (a mouthful!), which generally means that it is a protein that tells cells what to do, and in particular, IL-6 mediates the communication between immune cells.  It can have differing effects on the immune system, and can cause inflammatory responses or responses that protect the nervous system.  IL-6 has been found in the CSF of people with diseases such as TM, acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO), which is why it was chosen as the biomarker for this study.  A cut-off value of IL-6 was set at 10 pg/ml, meaning any concentration above this level was considered positive for IL-6.  They found CSF to be IL-6 positive in 40% of patients with TM and 51% of patients with other inflammatory neurological diseases, but only 3.9% of MS patient samples had CSF that was IL-6 positive, and none of the patients with non-inflammatory diseases or other demyelinating diseases like optic neuritis had CSF that was positive.  Although some people with MS had CSF that was positive for IL-6, levels were lower for these individuals than for those with TM or other inflammatory neurological diseases.  As a result of their findings, the authors believe that measuring IL-6 levels in CSF should be a screening tool used to rule out MS in individuals who present with MS-like symptoms who don’t actually have the disease.

Dr. Benjamin Greenberg, Director of the TM and NMO Centers at University of Texas Southwestern Medical Center in Dallas, commented on the lack of data in this study around treatment of MS relapses in the samples that were obtained within a month of an MS relapse, and whether treatments such as steroids could influence results.  Furthermore, there was incomplete information on the 10 patients that were categorized as having idiopathic TM, which if probed further could skew data.  Further studies will be needed to confirm whether or not measuring IL-6 levels is a useful diagnostic tool for differentiating MS from other inflammatory neurological diseases.

This summary was written by Gabrielle (GG) deFiebre, Research Associate at a Public Health non-profit in New York who was diagnosed with Transverse Myelitis in 2009. GG volunteers with the Transverse Myelitis Association. 

Original research: Wullschleger A, Kapina V, Molnarfi N, Courvoisier DS, Seebach JD, et al. (2013) Cerebrospinal Fluid Interleukin-6 in Central Nervous System Inflammatory Diseases. PLoS ONE 8(8): e72399. doi:10.1371/journal.pone.0072399