Immunosuppression: Use in Transplantation

Abstract

Clinical immunosuppression is the reduction of undesirable immunologic activity, usually achieved using immunosuppressive drugs. It is used in a variety of medical conditions, including inflammatory diseases and autoimmune disorders, but its most common application is in the field of organ transplantation. It has really been the advent of modern immunosuppression that has allowed for the growth and success of organ transplantation to the point where it now represents the standard treatment for many cases of end‐stage organ disease. The number of agents available for clinical use has increased significantly in the last two decades, with newer agents that more specifically target the involved portions of the immune system. Despite the advancements, however, the biggest challenge with immunosuppression remains the need to effectively balance immunosuppression to prevent rejection with the inherent toxicities associated with these medications.

Key Concepts:

  • Immunosuppressive therapy is a double‐edged sword; significant impact has been made on the prevention and treatment of rejection, but this has been associated with a significant increase in the risk of infections and certain types of malignancies.

  • Although steroids remain important immunusuprresive agents, because of their many side effects, recent efforts have focussed on how to minimise or avoid steroids completely.

  • Nephrotoxicity is the most important and troubling adverse effect of cyclosporine.

  • Tacrolimus is currently used widely worldwide in essentially all organ transplantation centres.

  • Adverse effects of tacrolimus and cyclosporine are similar, most commonly related to nephrotoxicity, neurotoxicity, impaired glucose metabolism, hypertension, infection and gastrointestinal disturbances.

  • Sirolimus and everolimus are not associated with the nephrotoxic side effects seen with the calcineurin inhibitors.

  • MMF is an antimetabolite and works to prevent proliferation of the stimulated T cell.

  • Antibody use, both polyclonal and monoclonal, has increased significantly in transplant.

  • Infection remains a major cause of morbidity and mortality after solid organ transplants.

  • Organ transplant recipients have an increased risk for developing certain types of de novo malignancies, including nonmelanomatous skin cancers, lymphoproliferative disease, gynaecologic and urologic cancers and Kaposi sarcoma.

Keywords: side effects; mechanism; immunosuppressive drugs; steroids; calcineurin; transplant

Figure 1.

Sites of action of new immunosuppressive drugs.

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How to Cite close
Suryavanshi, Dilip, Prabhakaran, Sangeetha, Matas, Arthur J, and Humar, Abhinav(May 2013) Immunosuppression: Use in Transplantation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001242.pub3]