Immunosuppression--an overview.

Abstract

The therapy of immune-mediated diseases in dogs and cats requires effective immunosuppressive therapy. The ideal therapy would suppress the abnormal (anti-self) immune responses while leaving the normal (anti-pathogen) immune responses intact. Unfortunately, such a therapy is not readily available. Current therapeutic strategies designed to suppress aberrant immune responses include combinations of glucocorticoids, cytotoxic drugs, and other immunomodulating agents such as cyclosporine and androgens. Glucocorticoids have a multitude of effects on the immune response at several levels and are both antiinflammatory and immunosuppressive. Cytotoxic drugs such as cyclophosphamide and azathioprine suppress the immune response by inhibiting protein (ie, antibody) synthesis, DNA replication, and cell division. Some cytotoxic drugs cause lysis of immunocompetent cells. Cyclosporine A suppresses production of interleukin-2, a cytokine necessary for the amplification stages of the immune response and critical for the activation of both T and B lymphocytes. Androgens modulate the immune system by as yet poorly defined mechanisms involving alterations in lymphocyte numbers and function as well as mononuclear-phagocytic cell function. Newer immunosuppressive agents are being studied in laboratory animals and human transplant patients that either inhibit do novo synthesis of nucleotides or signal transduction in lymphocytes, thereby reducing the number or function of immunocompetent cells. These newer agents can be combined with more traditional therapies for enhanced immunosuppressive effects.