Clinical use of immunosuppressive drugs to control the immune response

Abstract

It is increasingly clear that, regardless of etiology, inflammatory and immunological mechanisms are involved in the pathogenesis of virtually all hepatobiliary diseases and hepatic fibrogenesis. Studies of immunopathogenetic mechanisms have identified multiple therapeutic targets in both the innate and adaptive immune responses that portend the future ability to prevent hepatic allograft rejection and control progression of chronic viral hepatitis, alcoholic and nonalcoholic fatty liver disease, drug-induced hepatotoxicity, graft-versus-host disease (GVHD), and autoimmune and immune-mediated inflammatory diseases (IMIDs) of the liver. The current availability of multiple immunosuppressive and anti-inflammatory drugs with distinct, complementary sites of action provides the opportunity and impetus to study their therapeutic potentials in both transplant and nontransplant settings. Concurrent immunosuppression of several specific sites involved in immunopathogenesis may ultimately enhance efficacy, while minimizing the dosedependent toxicities of individual drugs. Thus, the goals of this chapter are to review the mechanism(s) of action of established and new immunosuppressive and anti-inflammatory agents and to discuss their current and future therapeutic potentials in the prevention of hepatic allograft rejection and nontransplant hepatobiliary diseases. © 2007 Humana Press Inc.