SENSITIVITY OF BABOON LYMPHOCYTES TO CYCLOSPORINE-A AND FK-506 - RELATIVE RESISTANCE OF ALLOACTIVATED CELLS TO CYA

The interspecies differences in CyA pharmacokinetics necessitate the establishment of optimal immunosuppressive doses in the baboon, especially as its use as host for preclinical xenografts is anticipated. We assessed the immunosuppressive effects of CyA and FK 506 on lymphocytes from chacma baboons, using human cells for comparison. At concentrations up to 100 mumol/l, neither drug was toxic to lymphocytes. FK 506 inhibited baboon and human lymphocyte proliferation and IL-2 synthesis equally. In contrast, approximately four times higher doses of CyA were needed to inhibit baboon lymphocytes responding to alloantigens. This may explain the inadequate immunosuppression of baboon graft recipients treated with clinically acceptable doses of CyA. We propose that CyA whole blood target levels of +/-1500 ng/ml should be used in this species and we provide evidence that chacma baboons are able to tolerate such doses without nephrotoxicity.