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Corticosteroids, the most widely known anti-inflammatory agents, increase the number of neutrophils in the blood but decrease their aggregation at inflammatory sites, decrease the number and function of other white blood cells, and inhibit cytokine production. They are most effective during an acute flareup of a chronic autoimmune disease and in conjunction with other agents because they do not adequately block autoantibodies when used alone.
Cytotoxic drugs kill all white blood cells and their precursors and were originally developed as anticancer agents. However, low-dose methotrexate is now known to be effective in reducing the symptoms and the need for corticosteroids in chronic inflammatory diseases such as rheumatoid arthritis, Crohn disease, psoriasis, and asthma.
Cyclosporine and tacrolimus are related to the cytotoxic drugs, but these drugs selectively inhibit helper T-cell production of interleukin-2, effectively preventing replication rather than killing them. They are used extensively to prevent rejection of transplanted tissue and graft-versus-host disease.
Intravenous gamma globulin (IVIG) is used routinely to replace antibodies in patients with immunodeficiency disorders. However, it also can be used as an immunosuppressive. IVIG inhibits phagocytosis of platelets in idiopathic thrombocytopenic purpura; it has been most successful in the treatment of children but also can produce a short-term remission in adults. Because it seems to inhibit natural killer cells and augment suppressor T cells, it also has been used to treat other autoimmune diseases, but its clinical effectiveness has not been determined.
Antilymphocyte antibodies inhibit the T-cell–mediated immune response. The two types are monoclonal antibodies, which react with one specific antigen, and polyclonal antibodies, which target several different antigens. Polyclonal antibodies are created by injecting animals (usually mice) with human lymphocytes. The animals' B cells are harvested from lymphoid tissue or peripheral blood and used to create antilymphocyte serum (ALS); isolated antibodies from these B cells are the active agents in antilymphocyte globulin (ALG). Both ALS and ALG are used routinely to treat transplant rejection and graft-versus-host reactions. Because they come from animals, however, they can cause serum sickness. In addition, they are not specific to T cells and also can destroy platelets.
Monoclonal antibodies are laboratory-created antibodies developed from a single cell line that block the receptor molecules that bind and transfer cytokine signals on T cells. OKT3, a monoclonal antibody obtained from mice, is a strong immunosuppressant used in the primary treatment of acute transplant rejection; it also may be effective in preventing rejection. It frequently causes a massive release of cytokines whose effects must be controlled, usually by corticosteroids, after the first or second dose. In addition, over time it stimulates the production of antimouse antibodies that block its effectiveness. Monoclonal antibodies provide disease or tumor-specific therapy for various autoimmune illnesses and cancers by selectively binding to tumor cell surfaces. Interleukin's effects are exerted on the T lymphocytes. Interferons have antiviral, antiproliferative and immunomodulary effects. See: hybridoma
Plasmapheresis, the separation and removal of plasma containing autoantibodies (AAb), is most effective against disorders in which the AAbs are tissue-specific, such as myasthenia gravis, and those in which more AAbs are found in the blood than in extravascular spaces.
CAUTION!Many immunosuppressant drugs increase patients' susceptibility to infections (e.g., the reactivation of tuberculosis) or the new acquisition of opportunistic infections. Some also increase the risk of developing malignant tumors, because of the loss of immunosurveillance.
Patients need to learn to minimize their exposure to infectious organisms and consistently to use good hand and oral hygiene measures. The medication regimen may be rigorous and should be accompanied by intensive teaching about desired effects and side effects of the drugs and the need for frequent bloodwork; written as well as verbal instructions about the treatment regimen is often provided to the patient.