Effects of free and liposomal FK506 on inflammatory cytokines in the hearts of EAM rats.

<p>Cytokine expression on day 21 after immunization was evaluated using real-time quantitative PCR. Relative expression of IFN-γ (A), IL-17 (B), TNF-α (C), IL-1β (D), IL-10 (E), IL-4 (F) and TGF-β (G) were normalized to GAPDH (N = 4–9 in each group). Data are expressed as the mean ± SEM. * P < 0.05 versus the saline treated group.</p

Effects of free and liposomal FK506 on histological findings in the myocarditic hearts.

<p>Representative transverse sections in ventricles stained with hematoxylin and eosin (upper panels) and Masson’s trichrome (lower panels) at low magnification (A) and high magnification (C). (B) Quantitative analysis of areas of cell infiltration and fibrosis (N = 4–12 in each group). Scale bars indicate 5mm and 500 μm in (A) and (C), respectively. Data are expressed as the mean ± SEM. * P < 0.05 versus the saline treated group. # P < 0.05 versus the free FK506 treated group.</p

Tissue distribution of free and liposomal FK506 in the rat EAM model.

<p>Tissue distributions of [³H]-labeled FK506 in the rat EAM model. Radioisotope activity in tissues was measured 2 hours after the single intravenous administration of free or liposomal [³H]-labeled FK506 on day 17 after immunization (N = 4 in each group). Data are expressed as the mean ± SEM. * P < 0.05 versus the free FK506 treated group.</p

Time-course changes in vascular permeability in myocarditic hearts in the rat EAM model.

<p>The representative brightfield and fluorescent images of the myocarditic hearts of rats that received fluorescent-labeled nano-sized beads (100 nm) are shown in the upper and lower panels, respectively. Hearts were excised on days 0, 10, 14, 17 and 21 after immunization. In each time point, 2–3 rats were checked. Bar indicates 10 mm.</p

Effects of free and liposomal FK506 on hemodynamic parameters in the rat EAM model.

<p>Quantitative data of hemodynamic parameters including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), max dP/dt and minimum dP/dt. EAM rats were treated with free or liposomal FK506 (0.035 mg/kg) on days 14 and 17 after immunization (N = 6 and 9, respectively). Data are expressed as the mean ± SEM. * P < 0.05 versus the free FK506 treated group.</p

Effects of free FK506 on hemodynamic parameters in the rat EAM model.

<p>Quantitative data of hemodynamic parameters, including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), max dP/dt and minimum dP/dt, on day 21 after immunization. Drugs were intravenously administered on days 14 and 17 after immunization. Rats were divided into Normal, EAM with saline treatment and EAM with free FK506 (0.035, 0.17 or 0.35 mg/kg) treatment groups (N = 5–15 in each group). Data are expressed as the mean ± SEM. * P < 0.05 versus the saline treated group.</p