Table 1.
Genetic and pharmacological modulation of tumor necrosis (TNF) signaling in animal models of multiple sclerosis (MS).
| EAE Model | |||||
|---|---|---|---|---|---|
| Clinical Score | BBB Permeability | Demyelination | Synaptic Dysfunction | ||
| Onset | Severity | ||||
| TNF-KO | ↑ 111; 112; 113; 116; 123; 122; 115 = 115 (T cell) 129 |
↑ 115; 114; 122 = 111; 112; 113 ↓ 129; 123; 116 115 (T cell) |
↓ 116 |
↑ 114; 122 = 111; 112 ↓ 123 115 (T cell) |
|
| anti-TNF therapy | = 120 (xpro1595- etanercept) |
= 119; 120 (xpro1595- etanercept) |
= 119 (xpro1595- etanercept) ↓ 120 (xpro1595- etanercept) |
↓ 137 (etanercept) 120 (xpro1595-etanercept) 136 (TNFR-Ig-ex vivo) 138 |
|
| TNFR1-KO | ↑ 122; 123; 133 |
↓ 122; 123; 133 |
↓ 122; 123; 133 |
↓ 133 |
|
| TNFR1-antagonism | ↑ 133 (Nanobody) = 120 (xpro1595- etanercept) 132 (ATROSAB) |
↓ 119; 120 (xpro1595-etanercept) 132 (ATROSAB) 133 (Nanobody) 117 (TNFRp55-IgG) |
↓ 119 (xpro1595-etanercept) 132 (ATROSAB) 133 (Nanobody) |
↓ 119 (xpro1595-etanercept) 132 (ATROSAB) 133 (Nanobody) |
|
| TNFR2-KO | ↑ 126 (monocytes) = 122; 98; 125; 129 ↓ 126 (microglial) |
↑ 129 122; 98; 123; 125; 126 (microglia) ↓ 126 (monocytes) |
↑ 98; 123; 122; 125; 126 (microglia) ↓ 126 (monocytes) |
↑ 98; 125;126 (microglia) ↓ 126 (monocytes) |
|
| TNFR2-agonism | ↑ 134 (sTNFR:Fc/p80) |
↓ 134 (sTNFR:Fc/p80) 135 (EHD2-sc-mTNFR2) |
↓ 135 (EHD2-sc-mTNFR2) |
↓ 135 (EHD2-sc-mTNFR2) |
|
| Cuprizone Model | |||||
| Demyelination | Remyelination | ||||
| TNF-KO | = 139 |
↓ 139 |
|||
| anti-TNF therapy | = 143 |
= 143 |
|||
| TNFR1-KO | = 139 |
↑ 139 |
|||
| TNFR1-antagonism | = 143 |
↑ 143 |
|||
| TNFR2-KO | = 139 |
↓ 139 |
|||
↑ increase; ↓ decrease; =no effect. Abbreviations: TNF, tumor necrosis factor; TNFR, TNF, tumor necrosis factor receptor; EAE, experimental autoimmune encephalomyelitis; BBB, blood–brain barrier; CPZ, cuprizone.