Immunomodulation

Abstract

Immunomodulation encompasses all therapeutic interventions aimed at modifying the immune response. Augmentation of the immune response is desirable to prevent infection in states of immunodeficiency, to fight established infections and to fight cancer. In immunodeficiencies, treatment of the cause is most important (e.g., malnutrition, HIV). Specific immune defects can seldom be corrected, and the establishment of a new immune system by allogeneic stem cell transplantation should be considered. To prevent infection, vaccination, is the most effective immunomodulatory technique. New tools to manipulate the response to vaccines involve the use of cytokines, viral vectors and even naked DNA. For the treatment of established infections, attempts to shift the immune response toward a Th1-type phenotype are desirable. For the treatment of cancer, efforts have focused mainly in making the cancer the preferred target of the immune system of the patient. To this effect, a variety of approaches have been used, including cytokines, anti-CTL-4, tumor-specific antibodies and cellular therapies using tumor infiltrating lymphocytes and even stem cell transplantation. In allergy, autoimmunity and organ transplantation the goal is to weaken the immune response. Selected allergies may be treated by specific desensitization. In autoimmunity and transplantation, drugs that blunt all immune responses are often used. A variety of drugs with different targets are used alone and in combination to induce immunosuppression. These agents interfere with antigen presentation (anti-CD 154, CTLA4-Ig), T-cell activation (calcineurin inhibitors, including cyclosporine A and tacrolimus), or T-cell proliferation (sirolimus, mycophenolate mofetil, leflunomide). Corticosteroids act at several levels of the immune response and also have significant anti-inflammatory properties. These drugs are necessary in solid organ transplantation to prevent rejection, or treat it if it ensues. When rejection proceeds despite the use of immuno-suppressive agents, the graft is lost and a new organ is required. In stem cell transplantation, the equivalent of rejection is graft vs host disease, a pathological condition where the newly acquired immune system recognizes the recipient as foreign and mounts an immune response against it. When graft vs host disease does not respond to steroids, the treatment options are very limited and the prognosis is poor. © 2006 Humana Press Inc.