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.


METHODS
In the present study, C57BL/J6 mice were immunized with 200 μg 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.


CONCLUSIONS
The findings suggest an adjunctive use of methotrexate in demyelinating disease.
Department of Pharmaceutical Sciences, Dibrugarh University, Assam, India.
Sandipan
S
Dasgupta
Bhaskar
B
Mazumder
Y Roja
YR
Ramani
Subhra Prakash
SP
Bhattacharyya
Mukesh K
MK
Das