**6.1 Corticosteroids**

Steroids have been the cornerstone of immunosuppression and remain important in treating episodes of acute rejection. However, newer treatment regimens are trying to minimize the use of steroids to avoid or minimize their adverse effects.

In pharmacologic or supraphysiologic doses, glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplant immunosuppressants to prevent acute transplant rejection and graft-versushost disease. Nevertheless, they do not prevent infection and also inhibit later reparative processes.

Glucocorticoids suppress cell-mediated immunity; they act by inhibiting the genes that encode the cytokines interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, and TNF-α. The inhibition of IL-2 is particularly important because it reduces T cell proliferation.

Glucocorticoids also suppress humoral immunity, causing B cells to express reduced amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis.

Glucocorticoids also stimulate the release of lipocortin-1 into the extracellular space, where it binds to leukocyte membrane receptors and inhibits the following inflammatory events: epithelial adhesion; emigration; chemotaxis; phagocytosis; respiratory burst; and the release of various inflammatory mediators including, but not limited to, lysosomal enzymes, cytokines, tissue plasminogen activator, and chemokines from neutrophils, macrophages, and mast cells.
