Immunosuppression of an Als in Relation to the Immunizing Lymphoid Antigen

AT A SIMILAR MEETING in] une of 1966, also held at Brook Lodge, we presented data from more than 200 canine experiments which were designed (8, 26, 27) to determine: 1) what magnitude of immunosuppression could be expected in dogs from treatment with small volumes of antilymphocyte sera (ALS) possessing high antiwhite blood cell titers, 2) what were the toxic effects of this kind of therapy, and 3) what were acceptable methods by which the globulin derivative (ALG) of ALS could be used clinically. The way in which the results of the animal investigations were translated into a clinical treatment protocol was also discussed at the same conference based upon the first experience with human recipients of renal homografts who were treated with adjuvant horse immune globulin. Including these early patients, we have now given intramuscular ALG, in combination with azathioprine and prednisone, to about 140 recipients of kidneys, livers, or hearts. The injections have not been directly responsible for any deaths. The benefits as well as the side effects of ALG have been analyzed from our case material on a number of occasions (11, 25, 27, 28) and will not be repeated here. Suffice it to say that after the addition of horse ALG to the therapeutic regimen in our institutions, the I-year survival after intrafamilial renal transplantation rose to more than 90 % and that after cadaveric renal transplantation to 83 %. In some of the liver recipients, of whom four have now lived for more than a year after operation, azathioprine was very greatly reduced and reliance was placed mainly on ALG and prednisone. Since ALG has been shown to be a potent immunosuppressive agent in every species including man in which it has been tested appropriately, there seems little reason to debate this issue in connection with organ transplantation in humans. However, a more legitimate inquiry has been raised by Hume et al. (7), namely, whether ALG is really needed in addition to azathioprine and prednisone for kidney transplantation, at least in their center. We will not dwell on this question since it has little to do with the points we wish to discuss here which are very simple and only three in number.