Fingolimod ameliorates chronic experimental autoimmune neuritis by modulating inflammatory cytokines and Akt/mTOR/NF‐κB signaling

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune‐mediated disease that targets the myelin sheaths of the peripheral nerves. Fingolimod is a sphingosine 1 phosphate (S1P) receptor antagonist with a high affinity for S1P receptors through the Akt–mTOR pathway, and prior research has suggested that it might be helpful in autoimmune illnesses. METHODS: Chronic experimental autoimmune neuritis (c‐EAN) was induced by immunizing Lewis rats with the S‐palm P0(180–199) peptide, and then the treatment group was intraperitoneally injected with fingolimod (1 mg/kg) daily. Hematoxylin and eosin staining was used to assess the severity of nerve injury. Immunohistochemistry staining showed that fingolimod's anti‐inflammatory effects on c‐EAN rats might be realized through the NF‐κB signaling pathway. Tumor necrosis factor‐α (TNF‐α), interferon‐γ (INF‐γ), interleukin‐1beta (IL‐1β), interleukin 6 (IL‐6), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule‐1 (ICAM‐1) were measured to evaluate the inflammation levels, and pAkt, p‐S6, and p‐p65 were used to measure the abundance of downstream activation markers to determine whether the Akt/mTOR/NF‐κB signaling pathway was activated in the c‐EAN model. RESULTS: Fingolimod treatment reduced the inflammatory reaction and the expression of NF‐κB in sciatic nerves. It also decreased the mRNA levels of the proinflammatory cytokines TNF‐α, IFN‐γ, IL‐1β, IL‐6, iNOS, and ICAM‐1 and pAkt, p‐S6, and p‐p65, representing the Akt/mTOR/NF‐κB signaling pathway. CONCLUSION: Our data showed that fingolimod could improve the disease course, alleviate the decrease in inflammation, and reduce proinflammatory cytokines through the Akt/mTOR/NF‐κB axis in c‐EAN rats, which could be beneficial for the development of CIDP‐related research.