Lymphocyte activation and correlation with IMPDH activity under therapy with mycophenolate mofetil

Background: In an attempt to monitor the pharmacodynamics of mycophenolate mofetil (MMF) we investigated the association of inosine morrophosphate clehydrogenase (IMPDH) activity in peripheral blood mononuclear cells with the expression of lymphocyte activation markers in stable cardiac transplant recipients treated with MMF. Methods: Twenty-four study patients were switched from azathioprine to MMF 7.2 +/- 4.1 years after heart transplantation. Results: While the MPA trough level remained unchanged, the mean activity of IMPDH declined from 890 to 462 pmol/10(6)PBMC/h three months after onset of MMF therapy, was almost completely inhibited at six months and partially restored to 160 pmol/10(6)PBMC/h 12 months after switch to MMF (p<.0001). We detected also significant changes in a number of activated lymphocyte subsets: CD4(+)/25(+), CD8(+)/38(+), CD19(+)/69(+), CD3(+)/16(+)/56(+), natural killer (NK) cells, and monocytes. Moreover, the IMPDH activity profile correlated positively with the number of CD8(+)/38(+) T cells (correlation coefficient (CC) +053), and inversely with NK cells (CC -0.52) and CD19(+)/ 69(+) cells (CC -0.61). Conclusions: We revealed a close association of IMPDH baseline activity in mononuclear cells with the expression of lymphocyte activation markers in stable heart transplant patients after introduction of MMF therapy. This supports the assumption of a rather immunomodulatory than immunosuppressive effect of MMF. (C) 2008 Elsevier B.V. All rights reserved.