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 monophosphate dehydrogenase (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) +0.53), 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.
Devyatko
Elena
E
Department of General Surgery and Transplantation, University Clinic of Surgery, Medical University Vienna, Vienna, Austria. yelena.devyatko@meduniwien.ac.at
Dunkler
Daniela
D
Bohdjalian
Arthur
A
Zuckermann
Andreas
A
Grimm
Michael
M
Muehlbacher
Ferdinand
F
Weigel
Guenter
G
D000328:Adult; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid