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

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

Immune checkpoint inhibitors

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A medication that inhibits the action of regulatory proteins, known as checkpoint proteins, on the immune response. Checkpoint inhibitors are used in the treatment of cancers which produce checkpoint proteins that reduce a patient’s intrinsic antineoplastic T-cell activity.