What are the mechanisms of action for immunosuppressive medications?

Updated: Oct 18, 2019
  • Author: Randy P Prescilla, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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The immunosuppressive properties of older agents were empirically discovered. Most of these agents were derived from microbial products. In general, these drugs exert their effects through a limited number of mechanisms.

  • Regulators of gene expression: The classic examples are glucocorticoids; others include vitamin D analogs and deoxyspergualin. Recent studies have shown that glucocorticoids affect inflammation by other (nongenomic) mechanisms.

  • Alkylating agents: Cyclophosphamide and other alkylate deoxyribonucleic acid (DNA) agents are mutagenic and can increase the risk of developing cancer.

  • Kinases and phosphatases inhibitors: These include cyclosporin A (CsA), tacrolimus (FK506), and sirolimus (SRL), which inhibit kinase cascades.

  • Inhibitors of de novo purine synthesis: The first-generation inhibitors are 6-mercaptopurine and azathioprine; the second-generation inhibitors are mizoribine and MMF. Potential third-generation enzymes include inhibition of inosine monophosphate dehydrogenase and inhibition of T lymphocyte–specific purine nucleoside phosphorylase. The polygentamate derivatives of methotrexate are antifolate compounds and inhibit de novo purine synthesis.

  • Inhibitors of de novo pyrimidine synthesis: These inhibitors include brequinar, leflunomide, and the structurally related malononitrilamides that inhibit dihydroorotate dehydrogenase.

Immunosuppression can be achieved by several mechanisms that affect lymphocytes such as depleting lymphocytes, diverting lymphocytic traffic, or blocking lymphocyte response pathways.

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