Immunoregulatory drugs: Mechanistic basis for use in organ transplantation

Manikkam Suthanthiran, Terry B. Strom

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Multiple immunoregulatory drugs, capable of constraining cell activation, differentiation, and/or proliferation, and each with distinct side effects, are currently used in the clinic to facilitate organ engraftment. Cyclesporine, azathioprine, corticosteroids, FK506 (tacrolimus), and RS61443 (mycophenolate mofetil) have already been approved by the United States Food and Drug Administration. Rapamycin (sirolimus), mizoribine, and 15-deoxyspergualin are being explored for their clinical efficacy. Based on their subcellular site of action, the immunosuppressants can be considered as: inhibitors of transcription (cyclosporine, tacrolimus), inhibitors of nucleotide synthesis (azathioprine, mycophenolate mofetil, miteribine), inhibitors of growth factor signal transduction (sirolimus), and inhibitors of differentiation (15-deoxyspergualin). Clearly, the transplant clinician now has a greater choice in the selection and application of immunosuppressants in the clinic for the fine regulation of anti-allograft immunity. The existing hypothesis regarding the mechanisms of action of immunosuppressants is that they all function to prevent allograft rejection by preventing/inhibiting cell activation, cytokine production, differentiation, and/or proliferation. A complementary supposition is that some of the immunosuppressants might regulate the anti-allograft repertory by stimulating the expression of immunosuppressive molecules and/or cells.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalPediatric Nephrology
Volume11
Issue number5
DOIs
Publication statusPublished - 1 Oct 1997

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Keywords

  • Anti-allograft response
  • Cytokines
  • Immunosuppressants

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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