Immunosuppressive drugs: Beyond glucocorticoids
Glucocorticoids are the most commonly used drugs for immunosuppression in dogs and cats with immune-mediated diseases. Prednisone in particular induces rapid, nonspecific inhibition of the immune system by reducing inflammation-associated gene transcription, inhibiting intracellular signaling pathways, downregulating cell membrane expression of adhesion proteins, and slowing cell proliferation. The inflammatory responses of most leukocytes—including neutrophils, macrophages, lymphocytes, and antigen-presenting cells—are blunted by glucocorticoids, so immunosuppression with this class of drugs downregulates both the innate and acquired immune systems.
The widespread use of organ transplants in people has motivated pharmaceutical companies to develop newer immunosuppressive agents that more specifically target the immune system and, thus, decrease the likelihood of adverse effects. When these agents are used in dogs and cats, the synergistic immunosuppressive effects may allow veterinarians to maintain disease remission with a lower glucocorticoid dose than would be possible otherwise. Because use of these alternative immunosuppressive drugs is increasing, veterinarians must be aware of those few studies that have evaluated the effectiveness, recommended doses, or prognosis when these drugs are administered in conjunction with or in place of prednisone. This article reviews the mechanisms of action and evidence-based rationale for using the most commonly recommended nonglucocorticoid immunosuppressive drugs and introduces medications that may eventually become standard-of-care for treatment of some immune-mediated diseases in veterinary patients.