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.
Photos by Greg Kindred
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Systemic immunosuppression is required to treat most small-animal autoimmune diseases; however, glucocorticoids, unfortunately,
modulate metabolic pathways in many nonimmune-system cell populations as well, possibly resulting in life-threatening side
effects. For example, prednisone has been associated with hypercoagulability, hypertension, increased susceptibility to opportunistic
infections, congestive heart failure, pancreatitis, and insulin resistance and secondary diabetes mellitus. In addition, although
the expected glucocorticoid-associated clinical signs of weight gain, alopecia, polyuria, polydipsia, and polyphagia are usually
only temporary annoyances in veterinary patients, some owners may find the inappropriate urination, continuous begging for
food, or pica to be intolerable, leading to frustration or even euthanasia.
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.
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