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 the pulmonary
vasoconstrition and vascular remodeling 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 monocrotaline (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 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.
Results
Sham MCT MCT+Thym
RV/LV, g/g 0.38±0.01 0.50±0.07 a 0.34±0.03 b
Lung/BW, g/kg 4.17±0.2 12.4±1.0 a 6.62±0.4 b
IL6 lung, AU 1.0±0.32 17.4±3.8 a 3.8±1.3 b
IL6 RV, AU 1.0±0.34 8.0±2.1 a 0.6±0.3 b
RVPmax, mmHg 25±2 56±8 a 24±3 b
dP/dtmax, mmHg/s 1231±108 1669±181 a 1191±90 b
RVEDP, mmHg 1.6±0.3 2.6±1.2 a 0.7±0.4 b
Chronic thymulin administration, started simultaneously with the first inflammatory
changes induced by MCT, completely reversed PH, 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:
World Congress of Cardiology, published in journal, European Heart Journal 2006; Vol.27(Suppl.1):901-902.