Effect of leflunomide on neurological function of guinea pigs with EAE and its immune mechanism

LYU Zhi-yu; YU Zhou; RONG Ben-bing; LI Zuo-xiao

doi:10.3969/j.issn.1002-266X.2015.25.008

Abstract：Objective To investigate the effect of leflunomide ( LEF) on neurological function of guinea pigs with ex-perimental allergic encephalomyelitis ( EAE) and the immune mechanism .Methods Fifty adult female guinea pigs were randomly divided into 5 groups with 10 rats in each group respectively , including high-dose LEF group , medium-dose LEF group, low-dose LEF group, EAE control group and normal control group .Rats in the low-, medium-and high-dose LEF groups were treated with LEF 10 mg/( kg· d) , 20 mg/( kg· d) and 40 mg/( kg· d) orally according to the body mass , once a day, seven days before the experiment and till the end .The score of neurological deficits in each group was recorded and we detected the proportion of CD4+CD2+5FOXP3 +regulatory T cels(Treg) cells in CD4+T cells by flow cytometry.Re-sult At the peak of onset , compared with the EAE control group , the score of neurological deficits was decreased , latency was prolonged and the development period was shortened in the high-dose and medium-dose LEF group (all P<0.05), and it was the most obvious in the high-dose group (P<0.05).At the peak of onset, compared with the normal control group, the proportion of CD4+CD2+5FOXP3 +Treg cells in CD4+T cells in CD4+T cells was decreased in the EAE control group (P<0.05); the proportion of CD4+CD2+5 FOXP3 +Treg cells was increased in the high-and medium-dose LEF group as compared with that of the EAE control group , and the high-dose LEF group was increased more significantly (P<0.05). Correlation analysis showed that the proportion of CD 4+CD2+5 FOXP3 +Treg cells in CD4+T cells of the EAE control group and LEF groups was negatively correlated with the score of neurological deficits ( r=-0.76, P=0.011; r=-0.66, P=0.000).Conclusions LEF can alleviate the symptoms of neurological deficits of EAE in guinea pigs , and the higher dose it takes, the better effect it has .Its mechanism may be that through increasing the proportion of peripheral blood CD 4+CD2+5 FOXP3 +Treg cells in CD4+T cells, it restores the immune suppression function .