Immunosuppressive agents have proved very useful in minimizing the occurrence or impact of deleterious effects of exaggerated or inappropriate immune responses. Unfortunately, these agents also have the potential to cause disease and to increase the risk of infection and malignancies.
Glucocorticoids (corticosteroids) were the first hormonal agents recognized as having lympholytic properties. Administration of
TABLE 55–1 Clinical uses of immunosuppressive agents.
any glucocorticoid reduces the size and lymphoid content of the lymph nodes and spleen, although it has no toxic effect on proliferating myeloid or erythroid stem cells in the bone marrow.
Glucocorticoids are thought to interfere with the cell cycle of activated lymphoid cells. The mechanism of their action is described in Chapter 39. Glucocorticoids are quite cytotoxic to certain subsets of T cells, but their immunologic effects are probably due to their ability to modify cellular functions rather than to direct cytotoxicity. Although cellular immunity is more affected than humoral immunity, the primary antibody response can be diminished, and with continued use, previously established antibody responses also are decreased. Additionally, continuous administration of corticosteroid increases the fractional catabolic rate of IgG, the major class of antibody immunoglobulins, thus lowering the effective concentration of specific antibodies. Contact hypersensitivity mediated by DTH T cells, for example, is usually abrogated by glucocorticoid therapy.
Glucocorticoids are used in a wide variety of conditions (Table 55–1). It is thought that the immunosuppressive and anti-inflammatory properties of corticosteroids account for their beneficial effects in diseases like idiopathic thrombocytopenic purpura and rheumatoid arthritis. Glucocorticoids modulate allergic reactions and are useful in the treatment of diseases like
Idiopathic thrombocytopenic Prednisone,1 vincristine, occasionally cyclophosphamide, mercaptopurine, or azathioprine; Usually good purpura (ITP) commonly high-dose gamma globulin, plasma immunoadsorption or plasma exchange
Autoimmune hemolytic Prednisone,1 cyclophosphamide, chlorambucil, mercaptopurine, azathioprine, high-dose Usually good anemia gamma globulin
Acute glomerulonephritis Prednisone,1 mercaptopurine, cyclophosphamide Usually good 1Drug of choice.
2Including systemic lupus erythematosus, rheumatoid arthritis, scleroderma, dermatomyositis, mixed tissue disorder, multiple sclerosis, Wegener’s granulomatosis, chronic active hepatitis, lipoid nephrosis, and inflammatory bowel disease. 3Basiliximab and daclizumab are approved for renal transplant only.
asthma or as premedication for other agents (eg, blood products, chemotherapy) that might cause undesirable immune responses. Glucocorticoids are first-line immunosuppressive therapy for both solid organ and hematopoietic stem cell transplant recipients, with variable results. The toxicities of long-term glucocorticoid therapy can be severe and are discussed in Chapter 39.