Fig. 4
REG differentially affects the number of CD115hi cells and the CCL2 levels in PB. Blood samples were collected according to the study design (Fig. 2A) and analyzed for CD115hi cells by FC, for CCL2 by ELISA, and for REG by liquid chromatography–tandem mass spectrometry. Empirical data (emp) were analyzed as described in the statistical methods section and the resulting estimates (est) are shown below the corresponding empirical graphs. A Steady-state analysis. Samples of the REG groups collected for PK analysis 1, 3, and 7 h after the last dose are omitted. V1 and V2 n = 6 animals/group; REG(V1) and REG(V2) n = 9 animals/group. Horizontal black lines represent mean values. Results of statistical tests on mean ratios for group comparison are tabulated. Significant P-values are indicated in bold. B PK/PD relationship analysis (n = 3 animals/group). Empirical data were analyzed as described in the statistical methods section and the resulting mean estimates with confidence interval (vertical bars) are presented below the corresponding empirical graphs as fold change relative to t0 for CD115hi and CCL2 and relative to Cmax for REG. The horizontal dotted black line represents the baseline. Confidence intervals completely below or above the baseline indicate significant changes. The relationship of REG with CD115hi and with CCL2 (PK/PD) is depicted based on the respective relative mean estimates.