Open AccessPharmacodynamics of T‐cell function for monitoring immunosuppression
Author(s) -
Barten M. J.,
Tarnok A.,
Garbade J.,
Bittner H. B.,
Dhein S.,
Mohr F. W.,
Gummert J. F.
Publication year - 2007
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2007.00413.x
Subject(s) - immunosuppression , proliferating cell nuclear antigen , pharmacology , il 2 receptor , pharmacodynamics , t cell , sirolimus , whole blood , interleukin 2 , medicine , cytokine , biology , immunology , immune system , pharmacokinetics , immunohistochemistry
. Objectives : Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T‐cell functions in heart transplant (HTx) recipients. Materials : PDs and blood concentrations (PK) of three different basis‐immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T‐cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL‐2, IFN‐γ) and surface antigen (for example, CD25) by FACS analysis. Results : In group I, at time points C0 and C2, increased CsA‐PK significantly inhibited expression of IL‐2, IFN‐γ, PCNA and CD25 ( P < 0.05). Correlations ( r 2 ) at C2 between inhibition of T‐cell functions (PD) with PK and with drug doses were: CsA‐PK: 0.71–0.91 and CsA‐dose: 0.73–0.87. In group II, increased TRL‐PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL‐2 and IFN‐γ expression was significantly higher on days 2 and 3 compared to PD effects of CsA ( P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL‐PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. Conclusions : Our results show that PD effects on T‐cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx.