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Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects. We investigated the effects of VPA in rats in which experimental autoimmune neuritis (EAN) had been induced (EAN rats). VPA (300 mg/kg, intraperitoneally) administration to EAN rats once daily immediately following immunization significantly suppressed mRNA levels of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-4, IL-6 and IL-17 in the lymph nodes of EAN rats. In peripheral blood and sciatic nerves of EAN rats, Foxp3(+) cells were increased but IL-17(+) cells were decreased during VPA treatment. Furthermore, suppressive and therapeutic treatment with VPA greatly attenuated both accumulation of macrophages, T cells and B cells, and demyelination in sciatic nerves, and greatly reduced the severity and duration of EAN. In summary, our data demonstrated that VPA could effectively suppress inflammation in EAN, suggesting that VPA could be a potent candidate for treatment of autoimmune neuropathies.

FTY720 (Fingolimod) is a novel type of immunosuppressive agent inhibiting lymphocyte egress from secondary lymphoid tissues thereby causing peripheral lymphopenia. FTY720 can inhibit macrophage infiltration into inflammatory lesions under pathological conditions. FTY720 has been clinically evaluated for prophylaxis of allograft rejection and treatment of multiple sclerosis, showing promising immunosuppressive effects. A robust inflammatory response after traumatic brain injury (TBI) plays an important role in the secondary or delayed injuries of TBI. Here we have investigated by immunohistochemistry in a rat TBI model the effects of FTY720 on early cell accumulation into the inflammatory tissue response and on expression of major histo-compatibility complex class II (MHC-II) and endothelial-monocyte activating polypeptide II (EMAP-II). Accumulation of MHC-II+ or EMAP-II+ cells became significant 1 day after injury and continuously increased during the early time periods. Further, double-staining experiments confirmed that the major cellular sources of MHC-II were reactive macrophages, however MHC-II+ cells only constituted a small subpopulation of reactive macrophages. Immediately after TBI, peripheral administration of FTY720 (1 mg/kg in 1 mL saline, every second day) significantly attenuated the accumulation of MHC-II+ macrophages from Day 1 to 4 and significantly attenuated the accumulation of EMAP-II+ macrophages/microglia at Day 4. Our findings show that FTY720 attenuates early accumulation of EMAP-II+ and MHC-II+ reactive monocytes following TBI, indicating that FTY720 might be a drug candidate to inhibit brain inflammatory reaction following TBI.