Introduction
Guillain–Barré syndrome (GBS) is a common autoimmune disease characterized pathologically by inflammation and demyelination in the peripheral nervous system (PNS) [1, 2]. Experimental autoimmune neuritis (EAN) is a classic animal model of GBS, which has been widely used in basic research of GBS [3, 4]. After activation, macrophages can be divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, and recently, new research found that M3 switch phenotype also existed [5, 6]. In GBS and EAN, M1 macrophages are involved in the inflammatory impairment of the myelin sheath through promoting cellular cytotoxicity and producing Th1 cytokines. M2 macrophages contribute to repairing myelin and axon by promoting Th2 immune response and the secretion of anti-inflammatory cytokines [7-9]. Several studies have demonstrated that the switch from M1 to M2 could effectively ameliorate the severity of EAN [7, 10, 11].
Nuclear factor-κB (NF-κB) is a inducible transcription factor expressed in a large number of cells and involved in immune and inflammatory responses [12]. Moreover, the activated form p65 of NF-κB has been observed in the sural nerve macrophages of acute and chronic inflammatory demyelinating polyneuropathy (AIDP, CIDP), and the sciatic nerves of rats with EAN, suggesting NF-κB attribute to the inflammatory demyelination. So far there are very few studies demonstrating the role of NF-κB in the course of macrophage polarized [13, 14]. However, the research results on the relationship between macrophages and NF-κB in this process have been controversial.
The objective of this study was to assess the effect of M2 macrophages in treating EAN and to explore the role of NF-κB regulating macrophage subtype. Our results showed that M2 macrophages is effective in treating EAN by inhibiting the activation of NF-κB p65 and the production of pro-inflammatory cytokines. The inhibitor of NF-κB, BAY11-7082 attenuates the severity of EAN by inhibiting NF-κB pathway and the polarization of M1 macrophages.