Evaluation of the role of erythropoietin and methotrexate in multiple sclerosis

Background: Erythropoietin, originally recognized for its role in erythropoiesis, has been shown to improve neurological outcome after stroke. Low-dose methotrexate is effective against certain inflammatory diseases, such as severe psoriasis and rheumatoid arthritis as well as Crohn's disease. Immunosuppressive effect of methotrexate also reduces the proportion of patients with chronic progressive multiple sclerosis with modest clinical benefits. Combination of erythropoietin and methotrexate can target neuroinflammation along with immunosupression. Objective: To evaluate the role of erythropoietin and methotrexate in experimental autoimmune encephalomyelitis, a commonly used animal model of several degenerative human diseases like multiple sclerosis. Materials and Methods: In the present study, C57BL/J6 mice were immunized with 200 mu g of myelin basic protein (MBP) emulsified in complete Freund's adjuvant (CFA) supplemented with 1 mg/ml of killed mycobacterium tuberculosis (MBP: CFA in 1: 1 ratio). These animals were given a combination of methotrexate and erythropoietin. Neurological function tests were scored daily by grading of clinical signs. Cerebral histopathology was performed to detect inflammatory infiltrates and demyelination. Results: Treatment with erythropoietin and methotrexate significantly improved the neurological function recovery, reduced inflammatory infiltrates, and demyelination as compared to controls possibly by stimulating oligodendrogenesis and down-regulating proinflammatory infiltrates. Conclusion: The findings suggest an adjunctive use of methotrexate in demyelinating disease.