Open AccessJournal Article
Purine metabolism and immunosuppressive effects of mycophenolate mofetil (mmf)
Anthony C. Allison,E M Eugui +1 more
TLDR
Clinically attainable concentrations of MPA suppress the proliferation of human arterial smooth muscle cells and may decrease the risk of lymphoma development and proliferative arteriopathy in long-term recipients of MMF.Abstract:
Mycophenolate mofetil (MMF) is a novel immunosuppressive drug that shows promise in preventing the rejection of organ allografts and in the treatment of ongoing rejection. Orally administered MMF is hydrolyzed by esterases in the intestine and blood to release mycophenolic acid (MPA), a potent, selective, noncompetitive inhibitor of the type 2 isoform of inosine monophosphate dehydroxygenase (IMPDH) expressed in activated human T and B lymphocytes. By inhibiting IMPDH, MPA depletes the pool of dGTP required for DNA synthesis. MPA has a more potent cytostatic effect on lymphocytes than on other cell types, and this is the principal mechanism by which immunosuppressive activity is exerted. MPA also depletes pools of GTP in human lymphocytes and monocytes, thereby inhibiting the synthesis of fucose- and mannose-containing saccharide components of membrane glycoproteins. These are recognized by the family of adhesion molecules termed selectins. By this mechanism, MPA could decrease the recruitment of lymphocytes and monocytes into sites of graft rejection. In addition to preventing allograft rejection, MMF suppresses graft-versus-host reactions in lethal and nonlethal murine models. MMF inhibits primary antibody responses more efficiently than secondary responses. MPA inhibits the proliferation of human B lymphocytes transformed by Epstein-Barr virus and is not mutagenic. Clinically attainable concentrations of MPA suppress the proliferation of human arterial smooth muscle cells. These two properties of MPA may decrease the risk of lymphoma development and proliferative arteriopathy in long-term recipients of MMF.read more
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CD4+CD25+ suppressor T cells: more questions than answers
TL;DR: The enhancement of suppressor-cell function might prove useful for the treatment of immune-mediated diseases, whereas the downregulation of these cells might be beneficial for the enhancement of the immunogenicity of vaccines that are specific for tumour antigens.
Journal ArticleDOI
Regulatory T Cells Induced by 1α,25-Dihydroxyvitamin D3 and Mycophenolate Mofetil Treatment Mediate Transplantation Tolerance
Silvia Gregori,Mara Casorati,Susana Amuchastegui,Simona Smiroldo,Alberto M. Davalli,Luciano Adorini +5 more
TL;DR: It is demonstrated that a short treatment with immunosuppressive agents, such as 1α,25-dihydroxyvitamin D3/mycophenolate mofetil, induces tolerance to islet allografts associated with an increased frequency of CD4+CD25+ regulatory cells that can adoptively transfer transplantation tolerance.
Journal ArticleDOI
Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Renal Transplant Study Groups
TL;DR: MMF proved superior to AZA as a posttransplant immunosuppressant in conjunction with cyclosporine and corticosteroids and performed consistently better for both MMF treatment groups at 3, 6, and 12 months.
Journal ArticleDOI
Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis.
Tak Mao Chan,Fu Keung Li,Colin S.O. Tang,Raymond Woon Sing Wong,Guo Xiang Fang,Yu Lian Ji,Chak Sing Lau,Andrew K.M. Wong,Matthew K.L. Tong,Kwok Wah Chan,Kar Neng Lai +10 more
TL;DR: In this paper, the authors compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months with those of a combination of cyclophosphamide and prednisoline given for 6 months.
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