tailieunhanh - Section X - Drugs Used for Immunomodulation

This chapter provides a brief overview of the immune response as background for understanding the mechanism of action of immunomodulatory agents. The general principles of pharmacological immunosuppression are discussed in the context of potential targets, major indications, and unwanted side effects. Four major classes of immunosuppressive drugs are discussed: glucocorticoids (see also Chapter 60: Adrenocorticotropic Hormone; Adrenocortical Steroids and Their Synthetic Analogs; Inhibitors of the Synthesis and Actions of Adrenocortical Hormones), calcineurin inhibitors, antiproliferative and antimetabolic agents (see also Chapter 52: Antineoplastic Agents), and antibodies | mofetil). Mycophenolate mofetil is replacing azathioprine as part of the standard immunosuppressive regimen after transplantation. At present, a number of centers are conducting various trials with new drug combinations including either cyclosporine or tacrolimus in combination with glucocorticoids and mycophenolate mofetil, with or without antibody-induction therapy. The array of new immunosuppressive agents is providing more effective control of rejection and permitting transplantation to become an accepted procedure with a number of different organs, including kidney, liver, pancreas, and heart. The apparent effectiveness of new drug combinations has resulted in a resurgence of interest in glucocorticoid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. Although new immunosuppressive agents are continuously under development, the ultimate goal of transplantation biology is immunologic tolerance. Drugs and protocols aimed at "fooling" the immune system to recognize nonself as self or to "retrain" autoimmune cells could provide true cures for these diseases. The other area of recent progress is in vaccine development. New approaches hold promise of potential immunization protocols that will be therapeutic, not only for a myriad of major infections (such as tuberculosis and HIV) but also for cancer and autoimmune diseases. New immunotherapeutic approaches will address not only the issue of specific drug toxicities and efficacies but also long-term economic, metabolic, and quality-of-life outcomes.