Mycophenolate mofetil treatment accelerates recovery from experimental allergic encephalomyelitis

Mycophenolate mofetil (MM) acts through its metabolite mycophenolic acid to inhibit inosine monophosphate dehydrogenase (IMPDH), an enzyme essential f or purine synthesis in lymphocytes. Oral treatment with MM from the day of immunization for 2 weeks significantly delayed both the development of acti ve experimental allergic encephalomyelitis (EAE) in Lewis rats and reduced the antibody response to myelin basic protein (MBP). MM did not deplete T a nd B cells, nor did it prevent induction of Th1 or Th2 cytokine in the regi onal nodes. Treatment of EAE with MM at the onset of clinical symptoms resu lted in more rapid recovery from EAE than in control or cyclosporin A (CsA) -treated. MM-treated rats had less infiltration of T cells, B cells, macrop hages and dendritic cells into brainstems than either the control or CsA-tr eated. MM-treated brainstems also had lower level of mRNA for Thl (IL-2, IL -12R ss2, IFN-gamma), Th2 (IL-4. IL-10) cytokines and TNF-alpha and TGF-ss compared to that in CsA and controls groups. This study shows MM was superi or to CsA in the treatment of EAE and acted by reducing the inflammatory in filtrate, not by suppression of Ig response or by promotion of regulatory c ells such as Th2 or Th3. (C) 2001 Elsevier Science B.V. All rights reserved .