Table 1.

Probable effects of disease-modifying therapies (DMTs) on microglia and/or monocyte-derived macrophages.

DMTs	Definition	Effect on microglia and/or monocyte-derived macrophages
Interferon-β	Cytokine released by host cell in response to viral infection and regulating immune responses (165)	- In MS patients, induces anti-inflammatory phenotype by reducing the production of nitric oxide and in contrast, increasing the expression of BDNF and Ig like transcript-3 in monocyte-derived MФs (166–168). Inhibits infiltration of monocyte-derived MФs into the CNS (169). - In EAE, upregulating IL-27 expression in monocyte-derived MФs leads to Th17 suppression (170) - In vitro, promotes phagocytosis capacity of microglia (126).
Glatiramer acetate	Synthetic amino acid polymer (15, 171)	- In MS, induces anti-inflammatory phenotype by inhibiting the production of nitric oxide in both microglia and monocyte-derived MФs. Enhances the phagocytic activity of microglia and monocyte-derived MФs (172, 173). Decreases microglial activation (174). - In EAE, promotes anti-inflammatory phenotype in monocyte-derived MФs by increasing the production of IL-10 and TGF-β and decreasing the secretion of pro-inflammatory cytokines and the expression of adhesion molecules (175). - In vitro, increases the production of IL-10 and reduces TNF-α in microglia (176).
Fingolimod	Agonist of sphingosine-1-phosphate (S1P) receptor (177)	- In MS, induces anti-inflammatory phenotype by inhibiting the production of pro-inflammatory cytokines and expression of pro-inflammatory miR-155 in monocyte-derived MФs. (116/1, 164.167/2) - In EAE, decreases CD40 expression and production of TNF in monocyte-derived MФs (178). - In vitro, switches M1 microglia to M2 phenotype (177).
Natalizumab	Anti-VLA-4 humanized monoclonal antibody (18)	- In MS, reduces microglia activation (179). - In EAE, suppresses the activated microglia and monocyte-derived MФs (180).
Dimethyl Fumarate	Methyl ester of fumaric acid (181)	- In MS, decreases the expression of pro-inflammatory mir-155 in monocyte-derived MФs (182). - In EAE, reduces the infiltration of monocyte-derived MФs in to the CNS (183) - In vitro, induces anti-inflammatory phenotype by inhibiting the production of nitric oxide and pro-inflammatory cytokines in microglia (184).
Teriflunomide	A reversible inhibitor of mitochondrial enzyme dihydrooratate dehydrogenase (DHODH) (185)	- In MS, induces anti-inflammatory phenotype by increasing the production of IL-10 and PDL-1 expression (186). - In EAE, inhibits the migration of monocyte-derived MФs in to the CNS (187, 188). - In vitro, induces anti-inflammatory phenotype in microglia by increasing IL-10 production (187, 189).
Rituximab	Chimeric Anti-CD20 monoclonal Ab (190)	- Inhibits monocyte activation by depleting GM-CSF expressing memory B cells (190).
Mitoxantrone	Cytotoxic agent of the anthracenedion family (191)	- In vitro, reduces migration capacity of monocytes (192).
Siponimod	Selective sphingosine-1-phosphate receptor modulator (193)	- In EAE, reduces the production of IL-6 and CCL5 in activated microglia (194) - In vitro, inhibits IL-6 production in siponimod-treated microglia (193).
Cladribine	Chlorodeoxyadenosine (CdA), is purine nucleoside analog (195)	- In vitro, inhibits the proliferation of microglia. Induces apoptosis in microglia (195)

MS, Multiple sclerosis, BDNF, Brain-derived neurotrophic factor; Ig, Immunoglobulin; CNS, Central nervous system; EAE, Experimental autoimmune encephalomyelitis; TH17, T helper type 17; IL-27, Interleukin-27; IL-10, Interleukin-10; TGF-β, Transforming growth factor-beta; TNF-α, Tumor necrosis factor-alpha; miR-155, microRNA-155; CD-40, Cluster of differentiation 40; VLA-4, Very late antigen-4; PD-L1, Programmed death-ligand 1; CD-20, Cluster of differentiation20; Ab, Antibody; GM-CSF, Granulocyte-macrophage colony-stimulating factor; IL-6, Inreleukin-6; CCL5, chemokine (C-C motif) ligand 5.