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Levels of interleukin-15-expressing blood mononuclear cells are elevated in multiple sclerosis
M Pashenkov1, M Mustafa, P Kivisäkk
1Division of Neurology, Neuroimmunology Unit, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Interleukin-15 (IL-15) is a novel IL-2-like cytokine expressed by cells of the monocyte/macrophage and epithelial lineages. Cytokines might be involved in the pathogenesis of multiple sclerosis (MS). Using immunocytochemistry, we analysed spontaneous expression of IL-15 by peripheral blood (PB) and cerebrospinal fluid (CSF) mononuclear cells (MNC) from patients with MS, other neurological diseases (OND) and healthy controls. IL-15- positive peripheral blood mononuclear cells (PBMNC) were elevated in patients with MS compared to healthy controls (P < 0.05). The elevation of IL-15- positive PBMNC was restricted to patients with chronic progressive MS and not observed in patients studied during the relapsing-remitting phase of MS. The numbers of IL-15- expressing PBMNC correlated with the duration and disability of MS (r = 0.45, P < 0.001, and r = 0.39, P < 0.01, respectively). IL-15 was undetectable in CSF MNC, and ELISA showed low CSF levels of IL-15 in occasional patients with MS and OND. IL-15 is a potent growth factor for gammadelta T cells, but there was no correlation between IL-15 expression by PBMNC and percentage of gammadelta T cells in blood from the MS patients. Together, these data demonstrate that IL-15 expression by PBMNC is upregulated in the chronic stage of MS.
Insights
Interleukin-15 (IL-15) is elevated in the blood of multiple sclerosis (MS) patients, particularly those with chronic progressive MS. This finding suggests IL-15 may play a role in the chronic stages of MS pathogenesis.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Cytokines, such as Interleukin-15 (IL-15), are implicated in the pathogenesis of neurological diseases.
- IL-15 is an IL-2-like cytokine produced by monocyte/macrophage and epithelial cells.
Purpose of the Study:
- To investigate the expression of IL-15 in mononuclear cells (MNC) from patients with multiple sclerosis (MS).
- To determine if IL-15 levels correlate with MS disease characteristics.
Main Methods:
- Immunocytochemistry was used to analyze spontaneous IL-15 expression in peripheral blood (PB) and cerebrospinal fluid (CSF) MNC.
- Patients included those with MS (chronic progressive and relapsing-remitting phases), other neurological diseases (OND), and healthy controls.
- ELISA was used to measure IL-15 levels in CSF.
Main Results:
- IL-15-positive peripheral blood mononuclear cells (PBMNC) were significantly elevated in MS patients compared to healthy controls.
- This elevation was specific to patients with chronic progressive MS, not relapsing-remitting MS.
- IL-15-expressing PBMNC numbers correlated with MS duration and disability.
- IL-15 was generally undetectable in CSF MNC and present at low levels in CSF of some MS and OND patients.
- No correlation was found between IL-15 expression and gammadelta T cell percentages in MS patients.
Conclusions:
- IL-15 expression in PBMNC is upregulated in the chronic stage of MS.
- IL-15 may contribute to the pathogenesis of chronic progressive MS.
- CSF IL-15 levels are not significantly altered in MS.