Corticosteroids, cytotoxic agents, and infection

Iatrogenic alteration of the immune system occurs with use of corticosteroids or noncorticosteroid immunosuppressants. Although there is overlap, noncorticosteroid immunosuppressants can be broadly divided into cytotoxic antineoplastic drugs and immunosuppressants used in transplantation. Because some of the cells or biologic pathways targeted by therapeutic immunosuppressive agents are essential for the body’s defenses against pathogenic microorganisms, the use of immunosuppressants involves walking a fine line between therapy and iatrogenic harm. The mechanism of action of the immunosuppressant, the dosage used, the length of therapy, and underlying disease(s) all affect the type and severity of subsequent infections. These factors also inform decisions on immunization, prophylaxis, or empirical therapy in high-risk patients. CORTICOSTEROIDS Mechanisms of immune suppression Corticosteroids exert a broad suppressive effect on the immune system. They achieve this in part by inhibiting transcription factors involved in activating proinflammatory genes, and also inhibiting lymphocyte activation, proliferation, and migration. Further, corticosteroids impair cytotoxic T-cell response and delayed-type hypersensitivity reaction. By reducing the production of interleukin-2, interferon-γ, leukotrienes, and tumor necrosis factor corticosteroids dysreguate the cytokine response to antigens. Adhesion molecules on endothelial cells are reduced and the migration of granulocytes to sites of infection is inhibited. Indirectly, corticosteroids impair phagocytosis due to their effect on glucose homeostasis. Antibody formation and turnover are also affected especially at high corticosteroid dosages and with prolonged use, and there may be reversible lymphopenia and monocytopenia.