Role of anti-interleukin-2 receptor antibodies in kidney transplantation

From the early 1960s, the mainstay of immunosuppression for kidney transpla ntation has been corticosteroids. Since then, many new drugs have been deve loped to maintain the renal allograft. Current maintenance immunosuppressio n commonly consists of corticosteroids, antiproliferative agents and calcin eurin inhibitors (e.g. cyclosporin). More recently, antihuman antibodies, e ither monoclonal or polyclonal, have been developed to use for induction at the time of transplantation or to treat rejection. With the advances in mo lecular technology, a new class of antihuman antibodies [the anti-interleuk in-2 receptor (IL-2R) antibodies] has emerged that incorporate a murine ant igen-binding site on to a human immunoglobulin backbone. Such methodology c reates antihuman antibodies with high affinity for the epitope and with pro longed serum antibody half-lives. Interleukin-2 and its receptor are central to lymphocyte activation and are the main targets of calcineurin inhibitors. In addition, the anti-IL-2R an tibodies inhibit a key target in immune activation. Daclizumab and basilixi mab have been shown to significantly reduce the incidence of acute,rejectio n in kidney transplantation. Since these anti-IL-2R antibodies are well tol erated and since. calcineurin inhibitors are intrinsically nephrotoxic, ant i-IL-2R antibodies have been used in an attempt to avoid cyclosporin after transplantation. Data from clinical trials seem to indicate that the additi on of an anti-IL-2R antibody is not sufficient to warrant complete withdraw al of calcineurin inhibitors for more than a very short period after transp lantation. A more promising role for anti-IL-2R antibodies may be in renal transplant recipients with delayed graft function (DGF). Recent data on the use of either low-dose calcineurin inhibitors or sirolimus (rapamycin) in conjunction with the anti-IL-2R antibodies for patients with DGF showed no increased risk of acute rejection. Long-term graft survival with use of the se low-dose calcineurin inhibitor protocols has yet to be established.