Figure 5

Cyclosporine A and tacrolimus differentially affect circadian rhythms in T-cell reactivity. Circadian rhythm of SEB-stimulated CD4 and CD8 T-cells in the peripheral blood of long-term transplanted patient taking cyclosporine A (n = 4) or tacrolimus (n = 5) determined over 24 hours at 8:00 a.m., 12:00 p.m., 8:00 p.m., 12:00 a.m. and the following day 8:00 a.m. Shown are the differences in absolute cell numbers of IFN-γ positive (A) CD4 and (B) CD8 T-cells with respect to the mean that was calculated from all values analyzed over the 24 h-time period (stippled line). In addition, relative CD4 (C) and CD8 (D) T-cell frequencies are shown. The variance of cytokine-producing T-cells at each time point with respect to this 24 h-mean is expressed as mean ± standard error of the mean. (E) Corresponding levels of calcineurin inhibitors in ng/ml determined from peripheral blood of the patients. Statistical analysis was performed using the repeated measures ANOVA with Tukey’s post-test. Statistically significant differences are indicated with respect to the 8:00 a.m. and 8:00 p.m. samples after drug-intake. The intake of calcineurin inhibitors (CNI) alone or in combination with methylprednisolone (MP) is indicated. *p < 0.05, **p < 0.01.