Table 1 The operative mechanisms of action of MIF and D-DT in MS, Alzheimer disease and glioblastoma and potential therapeutic anti-MIF/D-DT drugs that could block their pathogenic effects

Multiple sclerosis

• Induces leukocyte migration [52, 69]

• Activation of macrophages, astrocytes and microglia [48, 63,64,65,66,67]

• Promotes resistance of CD4( +) T cells to glucocorticoid treatment [68]

• Increases pro-inflammatory cytokine secretion [52, 64]

• Partial MHC class II constructs [66,67,68,69, 169,170,171,172,173,174,175,176]

• Ibudilast [52, 72, 161]

• ISO-1 [70]

Alzheimer disease

• Secreted by microglia near Aβ plaques [77, 78]

• Activation of astrocytes [79]

• Induces neurotoxicity [77, 85]

• ISO-1 [81, 112, 145, 146]

• Sulforaphane [120]

• Ibudilast [103, 148]

• mIR-608 [125]

• 4-IPP [140]

Glioblastoma

• Induces cell cycle progression, tumor growth, blockage of apoptosis [108, 109, 131]

• Induces angiogenesis and tumor spread [98]

• Inhibition of NK and T cell anti-cancer cytotoxicity [99,100,101,102,103]

• Promotes MDSCs and M2 macrophage polarization [99,100,101,102,103]

• ISO-1 [112, 145]

• shRNA MIF inhibitor [119]

• Monoclonal antibodies against MIF [118, 123, 145]