Mycophenolate mofetil
- Reversible inhibition of inosine monophosphate dehydrogenase → blockade of purine synthesis → selective inhibition of lymphocyte proliferation
- Indications
- Lupus nephritis
- Used in combination with cyclosporin or tacrolimus as transplant rejection prophylaxis
- Rheumatic diseases (glucocorticoid sparing)
- Adverse effects
- Infection (especially with CMV)
- Vomiting and diarrhea
- Hyperglycemia
- Hypertension
Calcineurin inhibitors
calcineurin = calcium- and calmodulin-dependent serine-threonine phosphatase
- Physiologically, calcineurin activates the nuclear factor of activated T cell (NFAT) by dephosphorylating its serine-threonine residues. Activated NFAT binds to DNA and enables transcription of a number of cytokines (most prominently, IL-2) and other molecules (e.g., VEGF). Transcription of IL-2 ultimately leads to activation of Th2, CD8 and NK cells.
- Agents
- Cyclosporine A, Tacrolimus (also FK-506 or fujimycin), Pimecrolimus
- Tacrolimus: immunosuppressant macrolide from Tsukuba
- Cyclosporine A, Tacrolimus (also FK-506 or fujimycin), Pimecrolimus
Glucocorticoids
- Mechanism of action
- Inhibition of intracellular NF-κB → inhibition of multiple inflammatory and immune mediators (e.g., cytokines) → suppression of B cells and T cells function
- Long-term effects (in hours) → direct influence on gene expression
- Increased apoptosis of eosinophils, T cells, and monocytes, perhaps by decreasing Bcl-2 expression