16.1. IMMUNOSUPPRESSIVE DRUGS
Immunosuppressive drugs are natural or synthetic substances which are used to induce inhibition of the immune system activity in order to prevent transplant rejection and suppress allergic reactions and autoimmune processes.
Immunosuppressive drugs have beenused in clinical practice for more than 50 years. The first drugs of this group include glucocorti-coids, antimetabolites, and alkylating agents. Absence of specificity in the mechanism of their action led to multiple side effects. Over the last years, pharmacologists developed novel immunosuppressive drugs inhibiting the immune system through a targeted effect exerted on specific mechanisms of the immune response; this has increased the effectiveness of therapy and reduced the number of unwanted reactions.
Mechanisms of suppression of the immune response are as follows.
• Inhibiting the expression of genes modulating the inflammatory response (glucocorticoids).
• Reducing the number of lymphocytes by means of cytotoxic drugs (antimetabolites, azathioprine, methotrexate, mycophenolic acid, leflunomide, and alkylating agents like cyclophosphamide).
• Inhibiting the signal activity of lymphocytes and thereby preventing their activation (cy-closporine, tacrolimus, sirolimus).
• Neutralizing cytokines and blocking their receptors necessary to transfer the immune response [inhibitors of tumor necrosis factor alpha: etanercept, infliximab, antibodies to interleukin(IL)-12 and to IL-23; inhibitors of cytokine and IL-1 receptor, inhibitors of IL-6 receptors].
• Reducing the number of the immune system cells by means of specific antibodies (poly-clonal antibodies: anti-thymocyte globulin; monoclonal antibodies: muromonab-CD3, basiliximab).