| Abstrakt: |
Recent multicenter, randomized clinical trials have shown that in renal transplant patients tacrolimus (FK506) was more efficient than cyclosporine A (CsA) at preventing acute rejection. In order to try and evaluate whether this difference was related to a different in vivo T-cell suppression we assessed, in a prospective study, the frequencies of interleukin (IL)-2-, IL-4-, IL-5-, IL-6-, IL-10-, interferon-gamma (IFN-Γ)- and double-positive IL-2/IFN-Γ-producing whole T cells, CD4+ and CD8+ T-cell subsets by means of cytokine flow cytometry. This was performed after in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol myristate acetate (PMA) and ionomycin, in the presence of monensin, in 14 healthy volunteers (controls) and in 14 renal transplant patients. The immunosuppression of the latter was based either on CsA (n=7) or on FK506 (n=7). Cytokine-expressing T-cell frequencies were assessed immediately pre-transplantation (D0), and subsequently 3 months (M3) and 6 months (M6) afterwards in fasting patients prior to the morning intake of the immunosuppressive drug. We found that at D0 the frequencies of IL-2- (22±2% vs. 22.2±2%), IFN-Γ- (26±3% vs. 29±3.4%) and IL-4- (0.8±0.2% vs. 1.4±0.2%)-expressing T lymphocytes were not significantly different between the controls and the patients, respectively. Conversely, the frequency of IL-2/IFN-Γ double positive cells was higher in the latter (9.3±1.6%) than in the controls (5.6±0.8); p=0.06. Finally, on D0 the frequencies of IL-5-, IL-6-, and IL-10-producing T lymphocytes were lower than 1% in both groups, as well as after grafting, i.e. on M3 and M6. As compared to baseline (D0): (a) chronic immunosuppression significantly decreased the frequencies of IL-2-, IL-4- and IL-2/IFN-Γ-expressing T cells, whereas those of IFN-Γ, IL-5, IL-6, and IL-10 were not significantly affected; (b) the frequencies of cytokine-expressing... [ABSTRACT FROM AUTHOR] |
