Resumo (PT):
Inflammation has an important pathophysiologic role in Pulmonary Hypertension (PH). Indeed, inflammatory cells recruitment and activation, with the release of cytokines (such as IL-6 and IL-1) and growth factors, may underlie pulmonary vasoconstrition and vascular remodelling that characterize PH. Thymulin, produced by thymic epithelial cells, is a nonapeptide neuroendocrine hormone with immunoregulatory actions, depressing C-C and CXC cytokines in the lung. In this study, we evaluated thymulin effects in a model of monocrotalin (MCT)-induced PH. Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. At D1, animals were randomly assigned to receive a subcutaneous injection of thymulin (10 ng/100g, qd for 3 wk) or saline. Three groups were analyzed: normal rats injected with saline (Sham, n = 7), MCT rats injected with saline (MCT, n = 9) and MCT rats treated with thymulin (MCT+Thym, n = 9). At the end of the third week, right ventricular (RV) hemodynamic parameters were measured: peak systolic RV pressure (RVPmax), peak rates of RV pressure rise (RV dP/dtmax) and RV end-diastolic filling pressures (RVEDP). Heart and lungs were weighted and samples were collected for for real-time PCR analysis of IL-6 mRNA levels. Results are summarized in the table below and expressed as means±SE. P<0.05: a vs Sham; b vs MCT. Chronic thymulin administration, started simultaneously with the first inflammatory changes induced by MCT, completely reversed PH and RV hypertrophy and attenuated IL6 activation. Thymulin immunomodulatory potential may thus be explored as a new therapeutic tool in PH management.
Language:
English
Type (Professor's evaluation):
Scientific
Notes:
79th Scientific Sessions of the American Heart Association, published in journal, Circulation. 2006; 114:753.