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 infec-tion and malignancies.
Glucocorticoids (corticosteroids) were the first hormonal agents recognized as having lympholytic properties. Administration of any glucocorticoid reduces the size and lymphoid content of the lymph nodes and spleen, although it has no toxic effect on prolif-erating myeloid or erythroid stem cells in the bone marrow.
Glucocorticoids are thought to interfere with the cell cycle of activated lymphoid cells. Glucocorticoids are quite cytotoxic to certain subsets of T cells, but their immunologic effects are prob-ably 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 anti-body responses are also 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 TDTH 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 ben-eficial effects in diseases like idiopathic thrombocytopenic purpura and rheumatoid arthritis. Glucocorticoids modulate allergic reac-tions and are useful in the treatment of diseases like asthma or as premedication for other agents (eg, blood products, chemother-apy) that might cause undesirable immune responses. Gluco-corticoids are first-line immunosuppressive therapy for both solid organ and hematopoietic stem cell transplant recipients, with vari-able results.