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  12 Other aspects of their use, generic products, therapeutic drug monitoring, and adverse effects will be addressed later in this chapter (Case 34-7, Question 9). Corticosteroids Prednisone, methylprednisolone, and prednisolone—all synthetic analogs of hydrocortisone—are the primary corticosteroids used to prevent and treat rejection of transplanted organs. These agents usually are given in fixed doses or dosing is based on body weight (mg/kg) despite the pharmacokinetic differences. Although they are an important part of immunosuppression, a goal of most transplantation programs is to minimize, eliminate, or avoid corticosteroid use because of their numerous and significant side effects. Corticosteroids have multiple effects on most cells and tissues of the body, but it is their anti-inflammatory and, more importantly, their immunosuppressive properties that serve as the basis for their use in organ transplant recipients. The corticosteroids bind with specific intracellular glucocor

  intercellular adhesion molecule (ICAM)-1 found on APCs, which bind with lymphocyte function-associated antigen expressed on the surface of T cells; ICAM-1 and ICAM-3 on APCs with CD2 on T cells; B7 (now called CD80 and CD86) on APCs with either CD28 or CTLA4 on T cells; and CD40 on APC with CD40 ligand (now called CD154) on T cells. The binding of costimulatory molecules is critical to T-cell activation. Without this costimulation, T cells undergo abortive activation or programmed T-cell death (apoptosis). Once recognition and costimulatory binding occurs, T-cell activation and proliferation are initiated. After interacting with class II antigens and stimulation from IL-1 secreted from macrophages, TH cells produce and secrete cytokines (e.g., interleukin [IL]-2 and interferon [INF]-γ). TH cells are classified according to their cytokine-secretion pattern into either TH1 or TH2 cells. TH1 cells secrete IL-2, INF, and tumor necrosis factor (TNF), which stimulate cytotoxic T cells (TC)