BLOCKADE OF THE INTERLEUKIN (IL)-2 IL-2 RECEPTOR PATHWAY WITH A MONOCLONAL, ANTI-IL-2 RECEPTOR ANTIBODY (BT563) DOES NOT PREVENT THE DEVELOPMENT OF ACUTE HEART ALLOGRAFT-REJECTION IN HUMANS/

Background. Anti-interleukin (IL)-2 receptor (IL-2R) antibodies have b een used as rejection prophylaxis after organ transplantation. Despite this induction treatment, acute rejections may occur, We wondered whe ther these rejections developed via the IL-2/IL-2R pathway, Methods. I n a prospective trial using BT563, a murine IgG1 anti-IL-2R antibody, for rejection prophylaxis after heart transplantation, 20 patients wer e treated in combination with cyclosporine from the day of transplanta tion (group A), As a control group, 31 patients were also treated with BT563, but in these patients, cyclosporine treatment was initiated on day 3 (group B), Results. Three patients from group A and two patient s from group B died in the first postoperative month (of causes not re lated to acute rejection) and were left out of the analysis of rejecti on incidence, Freedom from acute rejection at 1 week after transplanta tion in group A (14/17; 82%) was lower than in group B (16/29; 55%), a lthough the difference did not reach statistical significance, There w as no difference in either the number of acute rejection episodes at 1 2 weeks or the required rejection treatments between groups A and B. I nfectious complications were evenly distributed in both groups, Immuno histochemistry showed that during acute rejection, in the presence of circulating BT563, IL-2R-bearing cells were present in only one of fiv e rejection biopsies (20%), whereas these cells were often present (6/ 8, or 75%) in rejections occurring in the absence of BT563, The presen ce of BT563 was associated with a similar difference in the mRNA expre ssion of IL-2 (2/5 vs. 6/8). Conclusions. Apparently, despite adequate blockade of the IL-2/IL-2R pathway, patients may develop acute reject ion, reflecting the redundancy of the cytokine network, The ever-prese nt IL-15 may well be a candidate for overtaking the role of IL-2.