Mycophenolic acid (MPA) is an immunosuppressive agent, more and more extensively used in transplantation, rheumatology and nephrology. In this review, we will analyze the molecular mechanisms of its action, including the newest insights, in particular the inhibition of lymphocytes and the induction of tolerogenic dendritic cells (DCs) and its direct effects on non-immune cells (fibroblasts and myofibroblasts, mesangial cells, vascular smooth muscle cells [VSMC], endothelial cells). The latters suggest new therapeutic indications, specifically fibrosis (i.e. glomerulosclerosis and interstitial lung diseases), vascular damage and pulmonary hypertension, which represent key pathogenic features in connective tissue diseases. Given the differences in sensitivity to MPA among the various cell types and the great inter-individual variability in MPA pharmacokinetics, adequate daily doses and therapeutic drug monitoring may be decisive to ensure those MPA concentrations needed to switch off inflammation and restore peripheral tolerance in autoimmune disease (AID) patients. A warning on the severe adverse events strictly linked to immune suppression (i.e. progressive multifocal leukoencephalopathy [PML]) will be stressed.

Mycophenolic acid in rheumatology: mechanisms of action and severe adverse events

De Santis, M;
2010-01-01

Abstract

Mycophenolic acid (MPA) is an immunosuppressive agent, more and more extensively used in transplantation, rheumatology and nephrology. In this review, we will analyze the molecular mechanisms of its action, including the newest insights, in particular the inhibition of lymphocytes and the induction of tolerogenic dendritic cells (DCs) and its direct effects on non-immune cells (fibroblasts and myofibroblasts, mesangial cells, vascular smooth muscle cells [VSMC], endothelial cells). The latters suggest new therapeutic indications, specifically fibrosis (i.e. glomerulosclerosis and interstitial lung diseases), vascular damage and pulmonary hypertension, which represent key pathogenic features in connective tissue diseases. Given the differences in sensitivity to MPA among the various cell types and the great inter-individual variability in MPA pharmacokinetics, adequate daily doses and therapeutic drug monitoring may be decisive to ensure those MPA concentrations needed to switch off inflammation and restore peripheral tolerance in autoimmune disease (AID) patients. A warning on the severe adverse events strictly linked to immune suppression (i.e. progressive multifocal leukoencephalopathy [PML]) will be stressed.
Blood Vessels
Dendritic Cells
Drug Monitoring
Fibrosis
Humans
Immunosuppressive Agents
Leukoencephalopathies
Lymphocytes
Mycophenolic Acid
Myocytes, Smooth Muscle
Rheumatic Diseases
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/68429
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