Research: Cells making cytokines in MS

EpubRomme Christensen et al. Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2012 Sep 14;9(1):215.

BACKGROUND: Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce.
 
METHODS: We studied gene expression of a broad panel of cytokines in WB from relapsing-remitting multiple sclerosis (RRMS) patients in remission and healthy controls (HCs). Subsequently we determined the gene expression of the dysregulated cytokines in isolated PBMC subsets (CD4+, CD8+T-cells, NK-cells, B-cells, monocytes and dendritic cells) from RRMS patients and HCs and in CSF-cells from RRMS patients in clinical relapse and non-inflammatory neurological controls (NIND).
 
RESULTS: RRMS patients had increased expression of IFN-gamma (IFNG), interleukin (IL) 1-beta (IL1B), IL7, IL10, IL12A, IL15, IL23, IL27, lymphotoxin-alpha (LTA) and lymphotoxin-beta (LTB) in WB. In PBMC subsets the main sources of pro-inflammatory cytokines were T- and B-cells, whereas monocytes were the most prominent source of immunoregulatory cytokines. In CSF-cells, RRMS patients had increased expression of IFNG and CD19 and decreased expression of IL10 and CD14 compared to NINDs. CD19 expression correlated with expression of IL7, IL12A, IL15 and LTA whereas CD14 expression correlated with IL10 expression.
 
CONCLUSIONS: Using a systematic approach, we show that expression of pro-inflammatory cytokines in peripheral blood primarily originates from T- and B-cells, with an important exception of IFNG which is most strongly expressed by NK-cells. In CSF-cell studies, B-cells appear to be enriched in RRMS and associated with expression of pro-inflammatory cytokines; contrarily, monocytes are relatively scarce in CSF from RRMS patients and are associated with IL10 expression. Thus, our findings suggest a pathogenetic role of B-cells and an immunoregulatory role of monocytes in RRMS.


You can read the conclusions. Interferon gamma is a macrophage activator and in tissues is not considered good news as it can help macrophages destroy myelin. This comes from mainly natural killers celles rather than T cells as the immunologists would have us believe. Dacluzimab is thought have a major impact on NK cells and this maybe how it works rathher than attacking T cells. However when we look in the CSF there are more active B cells, is this because of EBV?,  They make IL-7 (remember the receptor for this confers increased risk to MS, which is an immune growth factor, IL-12 which activates macrophages and is also involved in growth of certain B cells and IL-15 is a factor that helps T cells and importasntly NK cell grow. Whilst IL-10 is consisdered to be be an anti-inflammatory cytokine it is also a B cell growth factor and may be there as part of the B cell response.

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