Table 2 Pro- and anti-inflammatory cytokines involved in MS pathogenesis and 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