Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycophenolate mofetil (MMF) is the morpholinoethyl ester of mycophenolic acid, which is its active metabolite. MMF is effective in prolonging survival of allografts and xenografts. However, little is known about the effects and the main mechanism of action of MMF in autoimmune diseases. In this study, the effect of MMF on the spontaneous disease progression in the MRL/lpr mouse model of lupus was examined. Eight-week-old MRL/lpr mice (n=18) were orally treated with MMF dissolved in a vehicle (90 mg/kg) once a day. Control animals received vehicle alone (n=17). The incidence of albuminuria (>300 microg/18 h) was significantly reduced by MMF treatment compared with vehicle-treated controls (cumulative incidence of albuminuria at 23 wk in MMF-treated mice; 22% versus 88% in controls; P=0.0001). The glomerulonephritis was histologically less severe in MMF-treated mice than in control mice (P=0.005). Furthermore, in immunofluorescence studies the amount of immunoglobulin and C3 deposits in the glomerular capillary wall was significantly less in MMF-treated mice (P < or = 0.002). Surprisingly, in vivo no clear-cut immune-modulating effects were observed because there were no differences between MMF-treated and control animals with regard to autoantibody formation. Also, spleen enlargement and numbers of CD3+, CD4+, and CD8+ T cells in spleen, lymph nodes, and peripheral blood were not different between both groups. Furthermore, no immunosuppressive properties of 90 mg/kg MMF were found in BALB/c mice on delayed-type hypersensitivity and primary antibody response to methylated bovine serum albumin. Interestingly, renal perfusion experiments revealed that binding of nucleosome/antinucleosome complexes to the glomerular basement membrane is decreased in MMF-treated mice compared with control mice. It is concluded that MMF suppresses the development of lupus glomerulonephritis and albuminuria in MRL/ lpr mice. The observed reduction of glomerular immunoglobulin deposits in MMF-treated mice and the renal perfusion studies indicate that MMF treatment leads to a decreased binding of immune complexes in the glomerular capillary wall in lupus nephritis.
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PMID:Attenuation of murine lupus nephritis by mycophenolate mofetil. 969 62

Mycophenolate mofetil is an immunosuppressive drug that is of established efficacy in renal transplantation. It inhibits the de novo pathway of purine synthesis and therefore lymphocyte proliferation. Mycophenylate mofetil has been shown to ameliorate the severity of renal injury in murine models of lupus nephritis. Recent studies suggest that it may also be effective in the treatment of patients with lupus nephritis when used in conjunction with steroids. These observations need to be confirmed in adequately sized randomised-controlled studies.
Lupus 2001
PMID:Treatment of systemic lupus erythematosus with mycophenolate mofetil. 1131 53

Overexpression of inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus glomerulonephritis. Mycophenolate mofetil (MMF), a novel immunosuppressive agent, is currently used in organ transplantation and under evaluation for treatment of autoimmune disorders. Mycophenolic acid, the active metabolite of MMF, has been shown to suppress cytokine-induced nitric oxide production in vitro. The aim of this study was to evaluate the effect of MMF on the expression of renal cortical iNOS mRNA and protection against glomerulonephritis in MRL/lpr mice. Three-month-old MRL/lpr mice (n = 6) displaying clinical symptoms of glomerulonephritis were treated for 3 months with MMF (90 mg/kg/day) dissolved in a vehicle. Controls were age- and sex-matched mice (n = 6) that received the vehicle alone. By reverse-transcription competitive polymerase chain reaction, we found that the renal cortical iNOS/beta-actin mRNA ratio was reduced by 30.8% (P <.05) in MMF-treated mice. Furthermore, MMF significantly reduced urinary nitrite production and degree of glomerulosclerosis. The glomerular volume was reduced by 17.5% (P <.001). Proteinuria was also significantly reduced in the MMF-treated group. However, by electrophoretic mobility shift assay, the nuclear binding of nuclear factor-kappaB (NF-kappaB) was not affected by MMF treatment. We conclude that in addition to its immunosuppressive action, MMF may reduce renal cortical iNOS mRNA expression and diminish glomerulosclerosis in MRL/lpr mice independent of modulation of the NF-kappaB pathway.
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PMID:Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/lpr mice. 1143 30

Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with superimposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3/10 with MMF alone and 1/10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9/13 and steroid dosage was reduced in 8/10 patients. Infections occurred in 3/13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.
Lupus 2001
PMID:The safety and efficacy of MMF in lupus nephritis: a pilot study. 1167 48

The treatment of severe lupus nephritis is based on the combination of steroids and cytotoxic drugs. Intravenous cyclophosphamide administered in "pulses" is effective in the induction of remission but other therapeutic alternatives are sought in refractory cases or severely relapsing patients. Mycophenolate mofetil, used in renal transplantation, also can be useful in severe lupus nephritis. We describe the evolution of 6 patients (5 women and 1 man; age 17-45 years) with severe lupus nephropathy who after achieving remission with intravenous cyclophosphamide and steroids (5 cases) or cyclosporin A (1 case) showed relapse of proteinuria and were treated with mycophenolate mofetil (dose 1000-2000 mg/day). Two patients have completed 24 months, 1 patient two cycles of 12 months, 2 patients 18 months and 1 patient 6 months. After this treatment, all patients have achieved remission (3 partial and 3 complete). There was no treatment failure and no one patient discontinued medication; however 1 case relapsed. There were no changes in leucocytes, haemoglobin, serum creatinine and serum albumin. ANA and alpha DNA antibodies decreased. Proteinuria (measured as protein/creatinine urine ratio: initial 3 and final 0.3) and dose of steroids (initial: 17.5 mg/d and final 5 mg/d) decreased significantly (p < 0.05 Wilcoxon t-test). The most common side effects were nausea and abdominal discomfort that improved without discontinuation of treatment. We conclude that mycophenolate mofetil is effective and a safe drug in severe relapsing lupus nephritis.
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PMID:[Mycophenolate mofetil in lupus nephritis]. 1198 81

Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ transplantation, is increasingly being used to treat autoimmune diseases including systemic lupus erythematosus (SLE). Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus nephritis. We evaluated the effect of MMF on the severity of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The mice were killed after 12 weeks of treatment. Treatment with MMF significantly decreased the amount of proteinuria, prolonged survival and reduced the histological severity of glomerulonephritis. Urinary nitrite/nitrate excretion in the MMF-treated mice was significantly reduced during the first 8 weeks of treatment. However, by the end of the 12 weeks' treatment period, there was no significant difference between vehicle and MMF-treated mice in terms of urinary nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS protein and induction of iNOS mRNA. We conclude that MMF is effective in attenuating the severity of nephritis in MRL/lpr mice. The beneficial effects of MMF on lupus nephritis during the early phase of the disease might be partly attributed to the inhibition of NO production. The inhibitory effect of MMF on NO production diminishes as the disease progresses. MMF probably has additional, as yet undefined mode of actions to fully account for its beneficial effects on lupus nephritis.
Lupus 2002
PMID:Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice. 1219 81

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensus that any one of these agents is more effective than another. Mycophenolate mofetil (MMF) is an immunosuppressive drug proven to be effective in reducing renal allograft rejection as well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.
Lupus 2003
PMID:Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome. 1294 24

Mycophenolate mofetil (MMF) is a potential new treatment for diffuse proliferative lupus nephritis. This study examines the clinical and histopathological effects, and potential mechanisms, of combination MMF/prednisone therapy in diffuse proliferative lupus nephritis. Nine patients with diffuse proliferative lupus nephritis confirmed by renal biopsy received MMF/prednisone for six months when repeat biopsies were performed. Clinical and histopathological parameters of activity and chronicity were studied. Collagens were detected by Sirus red staining; leucocyte phenotype, osteopontin (OPN), fibrinectin (FN), alpha-smooth muscle actin (alpha-SMA) and TGF-beta1 were detected by immunohistochemistry. The changes of clinical and histopathologic parameters were assessed and compared to histopathologic indicators. Eight of the nine patients achieved clinical remission; renal function deteriorated in one. Histopathological activity indices reduced significantly (9.56 +/- 2.83 versus 5.22 +/- 1.86, P < 0.01); however, the chronicity indices did not change (3.56 +/- 1.42 versus 3.22 +/- 1.20). T-cell and monocyte/macrophage infiltration. OPN expression and the percentage of proliferative cells in both glomerulus and tubulo-interstitium decreased significantly. Other features of chronic lesions, except for glomerular collagen deposition, did not change. In conclusion, MMF/prednisone therapy was effective for our patients with proliferative lupus nephritis. The active inflammatory lesions could be ameliorated through reduction of lymphocyte and monocyte/macrophage infiltration, inhibition of cell proliferation and downregulation of adhesive molecules. However, the chronic fibrotic lesions could not be significantly reduced.
Lupus 2004
PMID:Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study. 1499 4

Mycophenolate mofetil (MMF, CellCept) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation. MPA also inhibits the glycosylation and expression of adhesion molecules, and the recruitment of lymphocytes and monocytes into sites of inflammation. MPA depletes tetrahydrobiopterin and decreases the production of nitric oxide by inducible NO synthase without affecting the activity of constitutive NO synthases. Activated macrophages produce NO and superoxide, which combine to generate tissue-damaging peroxynitrite. By these two mechanisms MMF exerts anti-inflammatory activity. Unlike calcineurin inhibitors, MMF is not nephrotoxic and does not induce the production of TGFbeta, which is fibrogenic. MMF does not increase blood pressure, cholesterol levels or triglyceride levels in recipients. MMF reduces acute and chronic rejection in allograft recipients and is efficacious in some nephropathies. Evidence is accumulating that MMF may have clinical utility in some autoimmune disorders.
Lupus 2005
PMID:Mechanisms of action of mycophenolate mofetil. 1580 24

Mycophenolate mofetil (MMF) is an immunosuppressive agent used in transplantation, with evidence of superior protection against acute transplant rejection compared to azathioprine-containing regimens. Subsequently MMF has been used in a variety of autoimmune conditions. The major experience in systemic lupus erythematosus (SLE) has focused on proliferative lupus nephritis. Following its success in the treatment of lupus nephritis, MMF is now being used to control other SLE manifestations such as, lupus disease activity, haematological manifestations and resistant skin lupus. In this review, we discuss our own experience and the literature report about the use of MMF in SLE.
Lupus 2005
PMID:Mycophenolate mofetil and systemic lupus erythematosus: an overview. 1580 25


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