RAD001 (everolimus) attenuates experimental autoimmune neuritis by inhibiting the mTOR pathway, elevating Akt activity and polarizing M2 macrophages.

摘要: Guillain-Barre' syndrome (GBS) is an acute, postinfectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. As a classical animal model GBS, experimental autoimmune neuritis (EAN) has become well-accepted. Additionally, the potent immune modulation exerted by mammalian target rapamycin (mTOR) inhibitors been used to treat cancers showed beneficial effects. Here we demonstrate that mTOR inhibitor RAD001 (everolimus) protected rats from symptoms EAN, as shown decreased paralysis, diminished inflammatory cell infiltration, reductions in demyelination improved conduction. Furthermore, shifted macrophage polarization toward protective M2 phenotype modified milieu downregulating production pro-inflammatory cytokines including IFN-γ IL-17as well upregulating release anti-inflammatory such IL-4 TGF-β. Amounts downstream targets p-P70S6K p-4E-BP1 sciatic decreased, whereas level its upstream protein p-Akt was elevated. This demonstrated inhibited pathway encouraged expression p-Akt, which led polarization, thus outcome EAN rats. Consequently, exhibits strong potential therapeutic strategy for ameliorating poly-neuropathy.