From: The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology
Cytokine | Producer | Function | Role in MS | Therapies |
---|---|---|---|---|
IL-1α, 1β | DCs, NK, B cells, monocytes/macrophages, fibroblasts, etc | Pro-inflammatory: produced by dying cells (IL-1α) and inflammasome (IL-1β), both initiate inflammation [196] | Correlation with number and volume of cortical lesions and disease severity, especially IL-1β [167, 168] | Not reported |
IL-4 | Mast cells, eosinophils, basophils, | Immunomodulatory; Th2 differentiation; IgE production; tissue healing [190] | Possible correlation between IL4 gene polymorphism and MS susceptibility [194]; increased serum levels in MS and NMO [195] | Not reported |
IL-6 | T and B cells, macrophages | Pro-inflammatory; response to infection and tissue damage [160] | Elevated in MS CSF during acute phase[161]; correlation with disease severity [162] | Probably reduced upon GA treatment [160] |
IL-10 | Monocytes, Th2, Tregs, B cells, mast cells | Anti-inflammatory | Decreased in MS plasma [185]; decrease in CSF was correlated to worsened MS progression [187] | Modulated by ATX-MS-1467, mixture of MBP, in preclinical studies and MS ongoing trials [188, 189] |
IL-12/IL-23 | DCs | Generally pro-inflammatory; recent findings highlighted a possible neuroprotective role [94]; Th17 differentiation | SNPs-dependent increased MS susceptibility [150] | Ustekinumab (anti-IL-12/23p40) failed phase II trial on RRMS [151] |
IL-17 | Th17 | Pro-inflammatory; pathogens response, soluble factors production [142] | Increased IL-17 mRNA in CSF and IL-17 level in CNS lesions [148]; increased Th17 in MS CSF during exacerbations [149] | Ref. ustekinumab in IL-12/IL-23 |
GM-CSF | Macrophages, mast cells, NK, T cells, fibroblasts, etc | Cell differentiation and activation against pathogens and tissue damage [156] | Increase of GM-CSF-producing memory T cells in MS patients [157] | MOR103 (anti-GM-CSF) was well tolerated during phase 1b trial on SPMS and RRMS [158]. Ocrelizumab may improve MS course also by depleting GM-CSF-producing B cells [159] |
IFN-β | Monocytes, fibroblasts, endothelial cells, etc | Viruses response and defense; antigen-presentation induction; activation of NK and macrophages [174] | Mainly studied in EAE: IFN‐β − / − mice developed earlier and severe EAE [175, 176] | IFN-β1 is the main first-line RRMS treatment [179], acting by modulating T-cell differentiation, DCs migration and CKs production [181] |
IFN-γ | Activated B and T cells, mainly Th1 | Pro-inflammatory; activation of T, B cells and macrophages | Controversial: IFNγ administration worsened MS [152], but anti-IFNγ aggravated EAE in mice [154]. Possible protective role towards mature oligodendrocytes [155] | Not reported |