Immunosuppressive drugs: Beyond glucocorticoids


Immunosuppressive drugs: Beyond glucocorticoids

Prednisone is likely your go-to immunosuppressant. But because of associated adverse effects, having more options would help. Azathioprine, cyclosporine, mycophenolate mofetil, and leflunomide are commonly used for treating immune-mediated human diseases and may soon be incorporated into immunosuppressive protocols in veterinary medicine as well.
Aug 01, 2010

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
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.