Table 4.
Overview on supposed modes of action of approved therapeutics in MS and its proposed effects on the immune system.
| Substance | Administration | Mode of action | Effects on immune System |
|---|---|---|---|
| IFN-ß | SC, IM | Not elucidated in detail part of the type I interferon class (activation of JAK/STAT pathways) | pro-inflammatory lymphocyte activation ↓; anti-inflammatory lymphocyte activation↑; TH1 → TH2 shift; lymphocyte migration into CNS↓; monocyte activation↓ |
| GA | SC | Not elucidated in detail variety of immunological and non-immunological pathways Competition with myelin antigens for MHC binding site on APCs |
T cell autoreactivity to myelin antigens ↓; generation of GA-reactive TH2 cells; TH1 → TH2 shift; Tregs ↑; number of B cells, plasmablasts and memory B cells↓; shift from pro-inflammatory to anti-inflammatory B cell phenotypes |
| S1P | PO | functional antagonist of S1PR egress of lymphocytes from lymph nodes↓; effects on neuronal and glial cells in CNS | lymphocyte egression ↓; cytotoxicity ↓; regulatory T cells↑ |
| MTX | IV | type II topoisomerase inhibitor induction of cell lysis and initiation of programmed cell death on B cells and T cells | Levels of T cells and B cells↓; effects on innate immune system (macrophage proliferation) ↓; antigen presentation↓; antibody production↓; pro-inflammatory cytokine secretion↓ |
| TERI | PO | Inhibition of DHODH → reduction in de-novo pyrimidine synthesis and DNA replication of highly proliferating T cells and B cells↓ | Activated T cell and B cell proliferation ↓; Tregs↑; pro-inflammatory cytokines ↓ |
| DMF | PO | activation of Nrf-2 pathway inhibition of NF-κB pathway activation of HCAR2 | Nrf2↑; Tregs and CD56bright NK-cells↑; antioxidant proteins ↑; BBB migration ↓; TH1/TH17 → TH2 shift; pro-inflammatory cytokines ↓; apoptosis of T and B cells↑; Shift from pro-inflammatory to anti-inflammatory microglia |
| CLAD | PO | Purine nucleoside analog that interferes with DNA synthesis and repair, preferentially in activated lymphocytes | Lymphocytes ↓, relative increase in regulatory T cells |
| ALT | IV | mAb (IgG1) targeting CD52 predominantly on T cells and B cells, leading to cells lysis via CDC and ADCC | T cells and B cells ↓; CD56bright NK and Tregs↑; remodeling of lymphocytes |
| OCR | IV | mAb (IgG1) targeting CD20 on immature and mature B cells leading to cells lysis via ADCC > CDC | B cell depletion; regulatory B cells↑ |
| NTZ | IV | mAb (IgG4) targeting and inbiting α4 subunit of integrin molecules on leukocytes; | lymphocyte migration into CNS↓ |
IFN-, interferon beta; GA, glatirameracetate; S1P, sphingosine-1-phosphat receptor modulator (fingolimod, siponimod); MTX, mitoxantrone; TERI, teriflunomide; DMF, dimethylfumarate; CLAD, cladribine; ALT, alemtuzumab; OCR, ocrelizumab; NTZ, natalizumab; IM, intramuscularly; IV, intravenously; PO, orally; SC, subcutaneously; ADCC, antibody-dependent, cell-mediated cytolysis; CDC, complement-dependent cytolysis; DHODH, dihydroorotate dehydrogenase; HCAR2, hydroxycarboxylic acid receptor 2; mAb, monoclonal antibody; MBP, myelin basic protein; MMF, mono-methyl fumarate.