Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits the activity of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo synthesis of guanosine nucleotides. MMF has been used widely in solid-organ transplantation. Increased evidence indicated that MMF exhibited beneficial effects on various types of vasculitis, for reasons that were not fully understood. Endothelial cells play a pivotal role in the pathogenesis of vasculitis. Endothelium may not only be the main target for injury, but also be able to amplify the inflammatory response by adhesion molecule expression, leukocyte adhesion, cytokine production and angiogenesis. In the present study, the effect of mycophenolic acid (MPA), the active metabolite of MMF, on human umbilical vein endothelial cells (HUVECs) was investigated. MPA markedly inhibited tumor necrosis factor-alpha (TNFalpha)-induced intercellular adhesion molecule-1 (ICAM-1) mRNA and surface expression, suppressed TNFalpha-induced neutrophils adhesion to endothelial cells, and reduced TNFalpha-induced interleukin-6 (IL-6) secretion. The inhibitory effects of MPA on ICAM-1 surface expression and IL-6 secretion were not attenuated by addition of guanosine, implying that inhibition of these processes were not due to intracellular guanosine nucleotides depletion. MPA also decreased angiogenesis of endothelial cells in three-dimensional collagen gel culture system, reduced the migration in a wounded monolayer of endothelial cells, and inhibited the proliferation of endothelial cells. In conclusion, MPA exhibited multifarious effects on endothelial cells including inhibition of ICAM-1 expression, neutrophil attachment, IL-6 secretion, and the process of angiogenesis, which might contribute to the efficacy of MMF in the treatment of vasculitis.
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PMID:Effects of mycophenolic acid on endothelial cells. 1582 18

Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which affects de novo purine synthesis and T- and B-cell proliferation. So far its efficacy and safety as an immunosuppressive treatment have been proven in organ transplantations and also in various autoimmune diseases. A literature search was conducted by using PubMed and the Cochrane library. This review focuses primarily on current treatment with MMF for systemic lupus erythematosus, systemic sclerosis, vasculitis and idiopathic inflammatory myopathies.
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PMID:[Mycophenolate mofetil in the treatment of selected connective tissue diseases]. 2445 33

Mycophenolate mofetil (MMF) has been used in rheumatology for over 20 years. When transformed to the active metabolite of mycophenolic acid, it is a potent, selective, reversible inhibitor of inosine monophosphate dehydrogenase, a key enzyme of de novo purine synthesis, exerting a cytostatic effect on T and B cells. It also induces apoptosis of antigen-activated T cell clones, reduces the production of antibodies to inhibit the expression of adhesion molecules, reducing the influx of leukocytes and monocytes to inflammatory sites, and has anti-fibrotic properties. Although the main branch of medicine that uses MMF is transplantation, rheumatologists experienced in application of this drug confirmed its usefulness in the treatment of connective tissue diseases. In comparison with immunosuppressives available in rheumatology, MMF has a very good safety profile and is well tolerated by patients. Through multi-center, randomized, controlled clinical trials, MMF has become well established in the treatment of lupus nephritis. Conclusions about its effectiveness in other rheumatologic indications are not entirely clear, being derived from small clinical trials, observational studies and case reports. They suggest that MMF may also be used to treat extrarenal symptoms of SLE, interstitial lung disease in the course of SSc (systemic sclerosis), PM/DM (polymyositis/dermatomyositis), and skin lesions in these diseases, myositis and systemic vasculitis. It should be emphasized that MMF has proved effective in many cases complicated by multidrug resistance to immunosuppressive therapy and has allowed a significant reduction of long-term corticotherapy or its withdrawal.
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PMID:[Mycophenolate mofetil--20 years of experience in treatment of rheumatic diseases]. 2566 17

Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.
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PMID:The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis. 3152 31