An environment dominated by inflammatory cytokines favors polarization to M1 cells and inhibits an M2 switch. The consequences of this inhibition are not fully understood, but during EAE induction and progression, inflammatory factors have the potential to prevent recovery [110]. Elevated levels of inflammatory cytokines are also observed in human multiple sclerosis [105]. It is believed that inflammation contributes to axonal demyelination owing to neurotoxic cytokine effects on oligodendrocytes or inhibition of oligodendrocyte precursor cell proliferation and maturation [110]. This places M1 cells as key contributors to multiple sclerosis pathogenesis. Indeed, mice lacking IL-4 or IL-4Rα showed significantly worse EAE pathology [111]. The importance of IL-4 in EAE is also supported by observations that transduction with an IL-4 expressing viral vector reduced the symptoms of EAE [93,94]. Even though IL-4 has actions on other CNS cell types, its most potent effect is the induction of M2 microglia. Additionally, other M2 promoting cytokines, such as IL-33 [98] and IL-10 [96], have been shown to reduce the amount of demyelination [96] and improve clinical scores [98]. It is important to note that
