Background and purpose: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. The hallmark of this disease is an autoimmune neuroinflammation induced by autoreactive lymphocytes attack. Pervious documents indicated that phenytoin can protect axonal loss in EAE. Here, we investigated the immunomodulatory effects of phenytoin in EAE.

Materials and methods: In this experimental study, EAE was induced by guinea pig spinal cord homogenate and complete Freund’s adjuvant in Wistar rats. The animals were then divided into two therapeutic groups (n=7 per group). Phenytoin therapy (50 mg/kg-daily) was started in treatment group at day 12 when the treatment group developed a disability score. EAE control mice received vehicle alone on the same schedule. Signs of disability were monitored daily until day 36 when mice were sacrificed. Splenocytes were checked for proliferation by MTT test and cytokine production by ELISA.

Results: Phenytoin therapy after the occurrence of clinical symptoms significantly regressed the clinical symptoms and improved the weigh index of EAE rats. Phenytoin significantly decreased the production of pro-inflammatory TNF-α and IL-17 as well as IFN-γ in supernatant of spleen cells culture (P<0.001). However, the levels of anti-inflammatory IL-10 were not altered significantly. Lymphocyte proliferation significantly decreased in treatment group compared with that in control group (P<0.001).

Conclusion: In addition to direct neuroprotective effects, phenytoin can also improve EAE via modulation of immune responses.