Immunosuppressants

Cellular and molecular mechanisms of action

Manikkam Suthanthiran, Randall E. Morris, Terry B. Strom

Research output: Contribution to journalReview article

107 Citations (Scopus)

Abstract

The basic immunosuppressive protocol used in most transplant centers involves the use of multiple drugs, each directed at a discrete site in the T-cell activation cascade and each with distinct side effects. Cyclosporine, azathioprine, corticosteroids, FK506 (tacrolimus), and RS61443 (mycophenolate mofetil) have been approved by the Food and Drug Administration, and the clinical efficacy of rapamycin (sirolimus), mizoribine, 15-deoxyspergualin, and leflunomide is being explored. Based on their primary site of action, the immunosuppressants can be classified as inhibitors of transcription (cyclosporine, tacrolimus), inhibitors of nucleotide synthesis (azathioprine, mycophenolate mofetil, mizoribine, leflunomide), inhibitors of growth factor signal transduction (sirolimus, leflunomide), and inhibitors of differentiation (15-deoxyspergualin). Polyclonal antilymphocyte antibodies, monoclonal antibodies directed at the T-cell antigen receptor complex (OKT3, TIOB9), and monoclonal antibodies directed at additional cell surface antigens, including interleukin-2 receptor alpha, afford cell-specific regulation of the immune response and are being used in the clinical setting as induction therapy and/or antirejection drugs. Clearly, the transplant clinician now has a greater choice in the selection and application of immunosuppressants in the clinic for the fine regulation of the antiallograft repertory. The prevailing paradigm 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. One hypothesis, albeit provocative, is that some of the immunosuppressants might function by stimulating the expression of immunosuppressive molecules and/or cells.

Original languageEnglish
Pages (from-to)159-172
Number of pages14
JournalAmerican Journal of Kidney Diseases
Volume28
Issue number2
DOIs
Publication statusPublished - 1 Jan 1996
Externally publishedYes

Fingerprint

leflunomide
Immunosuppressive Agents
Tacrolimus
Sirolimus
Mycophenolic Acid
Azathioprine
Cyclosporine
Interleukin-2 Receptor alpha Subunit
Transplants
Muromonab-CD3
Antilymphocyte Serum
United States Food and Drug Administration
Surface Antigens
T-Cell Antigen Receptor
Pharmaceutical Preparations
Immunosuppression
Allografts
Signal Transduction
Intercellular Signaling Peptides and Proteins
Adrenal Cortex Hormones

Keywords

  • antiallograft response
  • cytokines
  • Immunosuppressants
  • monoclonal antibodies

ASJC Scopus subject areas

  • Nephrology

Cite this

Immunosuppressants : Cellular and molecular mechanisms of action. / Suthanthiran, Manikkam; Morris, Randall E.; Strom, Terry B.

In: American Journal of Kidney Diseases, Vol. 28, No. 2, 01.01.1996, p. 159-172.

Research output: Contribution to journalReview article

Suthanthiran, Manikkam ; Morris, Randall E. ; Strom, Terry B. / Immunosuppressants : Cellular and molecular mechanisms of action. In: American Journal of Kidney Diseases. 1996 ; Vol. 28, No. 2. pp. 159-172.
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