Immunosuppressive Therapy

Immunosuppressive therapy becomes necessary when immune mediated tissue damage is life-threatening or causes organ dysfunction. For the horse patient, few immunosuppressive drugs have been studied and are used clinically, including: (a) inhibitors of gene expression or transcription (e.g., corticosteroids); (b) inhibitors of nucleotide synthesis (e.g., azathioprine, methotrexate); (c) alkylating agents (cyclophosphamide, chlorambucil, vincristine); (d) phosphatase and kinase inhibitors (e.g., cyclosporine A, tacrolimus, rapamycin); and (e) monoclonal antibodies (e.g., against B cell molecules). Glucocorticoids also decrease degranulation of eosinophils and basophils/mast cells. The effect on neutrophil phagocytosis and bactericidal activity has been variable, depending on the experimental system used (in vivo versus in vitro), but it seems dose-dependent. Potential adverse effects of systemic cyclosporine reported in human patients include: vasoconstriction; hypertension; nephrotoxicity (renal failure, hyperkalemia); hepato-toxicity; diarrhea; hyperlipidemia; hyperglycemia; neurotoxicity (tremors, seizures, coma); hirsutism; and potential susceptibility to infectious organisms that require cell-mediated protection.