Mycophenolate mofetil improves neurological function and alters blood T-lymphocyte subsets in rats with experimental autoimmune encephalomyelitis.
OBJECTIVE
This study evaluated the clinical and pathological effects of the immunosuppressive agent mycophenolate mofetil (MMF) in rats with experimental autoimmune encephalomyelitis (EAE; a model of multiple sclerosis [MS]).


METHODS
EAE rats were randomly divided into 4 groups: model alone (n = 7); low- or high-dose MMF (20 and 30 mg/kg per day, respectively, n = 6 each) orally for 14 days; methylprednisolone (20 mg/kg per day, n = 6) injected once daily for 3 days. Six normal Wistar rats served as controls. Clinical signs and histopathological findings were evaluated 14 days after treatment started.


RESULTS
Oral administration of high-dose MMF significantly ameliorated the course of EAE in rats: cumulative clinical scores were lower and weight loss was less than in rats receiving methylprednisolone. The ameliorated disease course was associated with alleviation of histopathological signs of EAE. Treatment increased the blood proportion of CD8(+), CD4(+)CD25(+) and CD4(+)CD45RA(+) T cells, with a concomitant reduced proportion of CD4(+) T cells and ratio of CD4(+) to CD8(+) T cells, compared with EAE model alone rats.


CONCLUSIONS
MMF may have pharmacological potential in MS treatment and these findings may help in understanding the pathophysiological mechanism of MS.
Department of Neural Medicine, Second Hospital of Shandong University, Jinan, China.
Zhengyu
Z
Zhu
Wei
W
You
ZhaoHong
Z
Xie
Ping
P
Wang
Zhen
Z
Liu
Cunfu
C
Wang
JianZhong
J
Bi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006168:Guinea Pigs; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D018655:Lymphocyte Count; D008775:Methylprednisolone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D007168:IMP Dehydrogenase; D017493:Leukocyte Common Antigens; D009173:Mycophenolic Acid; D008775:Methylprednisolone
Mycophenolate mofetil; T-lymphocyte subsets; experimental autoimmune encephalomyelitis; multiple sclerosis