Conversion from cyclosporin A to tacrolimus is safe and decreases blood pressure, cholesterol levels and TGF-beta 1 type I receptor expression

To determine whether conversion from cyclosporin A (CsA) to tacrolimus (TAC )-based immunosuppressive therapy is safe and might lead to improvement in the clinical side effect profile we studied 55 cardiac allograft recipients . Ten stable patients were electively converted (0.2-1.5 yr after transplan tation; group 1) and 45 patients were converted on indication (0.5-14 yr af ter transplantation; group II). We studied blood pressure, cholesterol leve l and renal function in all patients. To unravel the mechanisms by which Cs A may exert its toxic effects and to evaluate whether conversion is associa ted with immune activation, we analyzed the transforming growth factor (TGF )-beta1 system and intragraft interleukin (IL)-2 and IL-15 mRNA expression by real-time reverse transcription-polymerase chain reaction (RT-PCR) and q uantitative flow cytometry in the selectively converted patients (group I). Conversion did not result in immune activation as no clinical, histological or molecular signs of immune activation (increased intragraft IL-2 and IL- 15 messenger RNA (mRNA) expression) leading to rejection were found. It did not improve renal function neither in patient group I nor in patient group II. However, after conversion the blood pressure decreased (group I: systo lic 154 +/- 16 vs 143 +/- 21 mmHg, p = 0.03, diastolic: 99 +/- 11 vs 90 +/- 11, p = 0.02 and group II: systolic 155 +/- 17 vs 142 +/- 14, p < 0.001, d iastolic: 99 +/- 11 vs 91 +/- 8 mmHg, p < 0.001). Likewise, the cholesterol levels improved (group 1: 6.6 +/- 0.5 vs 5.7 +/- 0.3 mmol/L, p = 0.001 and group II: 7.1 +/- 1.7 vs 6.1 +/- 1.7 mmol/L, p = 0.001). When patients wer e treated with TAC the ongoing rejections (n = 4) resolved and gum hyperpla sia disappeared (n = 5). Conversion was associated with a two-fold lower TG F-beta1 type I receptor expression on peripheral lymphocytes and monocytes (p = 0.02 and p = 0.002, respectively). Conversion from CsA to TAC results in improvement of blood pressure and cho lesterol levels and does not induce immune activation. These beneficial eff ects were accompanied with lower TGF-beta1 type I receptor expression.