The immunomodulating effects of interferons have led to their use in the treatment of a variety of illnesses, including cancer (1), and virally mediated infections, such as hepatitis (2). In addition, IFN has been given to immunosuppressed patients in an attempt to reconstitute the immune response to prevent viral infections such as CMV and herpes Simplex (3). Since CMV and viral hepatitis are potentially serious complications of renal transplantation (3, 4), the use of IFN for prophylaxis or treatment has been advocated in this setting. However, the potential effects of giving an immuno-modulator such as IFN to immunosuppressed transplant patients raises theoretical concerns about activation of immune responses and an increased risk of allograft rejection.
Current immunosuppressive regimes for renal transplantation include CsA or FK506 in combination with steroids and sometimes AZA. While the mechanisms of action of CsA and FK506 are not completely understood, these agents appear to inhibit T cell activation through binding to specific binding cellular proteins (immunophilins), thereby altering intracellular signaling pathways and ultimately inhibiting expression of IL-2 and other cytokines (5). Both CsA (6) and FK506 (7) may inhibit IFN production, and low levels of circulating IFN-α have been described in renal transplant recipients (8). Although IFN modulate the immune response-both at the level of T cell activation (9) and antigen expression (10), the exact roles of these compounds in the immunosuppressive action of CsA and FK506 are not known.
A number of studies have claimed efficacy of IFN-α preparations in the treatment of chronic persistent hepatitis (2) and trials of IFN preparations for viral prophylaxis in renal transplant recipients have been reported (3, 11, 12). The results of such trials suggested a benefit of prophylaxis for viral infections (3, 11), but, at times, at the expense of increased rejection (12). The complex issues involved in using IFN to treat hepatitis in a transplanted, immunosuppressed population prompted us to review our experience with IFN-α treatment in renal transplant patients.