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Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis
V Navikas1, D Matusevicius, M Söderström
1Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Insights
Interleukin-6 (IL-6) mRNA-expressing cells are elevated in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients, suggesting a role for IL-6 in this neurological disease. Further research is needed to clarify IL-6
Area of Science:
- Neuroimmunology
- Cytokine research
- Multiple Sclerosis pathogenesis
Background:
- Increased intrathecal immunoglobulin production in multiple sclerosis (MS) suggests involvement of B cell activating factors.
- Interleukin-6 (IL-6) is a cytokine known to induce immunoglobulin production by activated B cells.
Purpose of the Study:
- To measure Interleukin-6 (IL-6) mRNA-expressing mononuclear cells (MNC) in the blood and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS).
- To investigate the role of IL-6 in the context of MS and other neurological conditions.
Main Methods:
- In situ hybridization (ISH) using synthetic oligonucleotide probes was employed to quantify IL-6 mRNA-expressing MNC.
- Samples were analyzed from patients with MS, aseptic meningo-encephalitis (AM), other neurological diseases (OND), and healthy subjects.
- Cell cultures were stimulated with myelin basic protein and proteolipid protein.
Main Results:
- IL-6 mRNA-expressing MNC were significantly elevated in the blood and CSF of MS patients compared to controls.
- Elevated levels of IL-6 mRNA-expressing MNC were also observed in the blood of AM patients.
- Cultivation with myelin basic protein and proteolipid protein strongly augmented IL-6 mRNA-positive cells in MS samples.
Conclusions:
- IL-6 is upregulated in multiple sclerosis (MS), particularly within the cerebrospinal fluid (CSF).
- These findings suggest IL-6 is one of several cytokines implicated in MS pathogenesis.
- The precise role of IL-6, whether disease-promoting or protective, in MS remains undetermined.
Abstract:
The increased intrathecal production of immunoglobulins within the cerebrospinal fluid (CSF) compartment commonly observed in multiple sclerosis (MS) implicates participation of B cell activating factors. One effect of the cytokine interleukin (IL)-6 is induction of immunoglobulin production by activated B cells. Employing in situ hybridization (ISH) with synthetic oligonucleotide probes, we measured numbers of IL-6 mRNA-expressing mononuclear cells (MNC) in blood and CSF from patients with MS, aseptic meningo-encephalitis (AM), and in blood from patients with other neurological diseases (OND) and healthy subjects. Numbers of IL-6 mRNA-expressing MNC were elevated in blood (mean frequency 1 per 33,000 MNC) and even further enriched in the CSF (1 per 10,000 MNC) of MS patients, and to a similar extent in AM patients' blood. Cultivation in the presence of myelin basic protein and proteolipid protein revealed strong augmentation of IL-6 mRNA-positive cells in MS but not in OND. The results suggest that IL-6 is one of several cytokines which are upregulated in MS, in particular locally in the CSF. A role of IL-6 in MS, whether disease- promoting or protective, remains unclear.
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