Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance.

C57BL/6 mice infected with Trypanosoma cruzi, the causal agent of Chagas' disease, develop severe thymocyte depletion paralleled by an inflammatory syndrome mediated by tumor necrosis factor-alpha (TNF-alpha). The exacerbated inflammatory reaction induces the activation of hypothalamus-pituitary-adrenal (HPA) axis with the consequent release of corticosterone (CT) into the circulation as a protective response. Thymocyte apoptosis has been related to a rise in TNF-alpha and CT levels, and both mediators are increased in T. cruzi-infected C57BL/6 mice. The depletion of immature CD4(+)CD8(+) thymocytes by apoptosis following infection with the parasite was still present in mice defective in both types of TNF-receptors (double knockout). However, thymic atrophy was prevented by adrenalectomy combined with RU486 administration, demonstrating that this is a CT-driven phenomenon. Our results put emphasis on the importance of an appropriated immuno-endocrine balance during T. cruzi infection and show that functional deviations in the immuno-endocrine equilibrium have profound effects on the thymus and disease outcome.

Effects of long-term propranolol and octreotide on postprandial hemodynamics in cirrhosis: a randomized, controlled trial.

BACKGROUND & AIMS: Postprandial increases in portal pressure may influence esophageal variceal rupture. The effects of chronic propranolol and octreotide (100 and 200 microg subcutaneously in a single dose) on postprandial hemodynamics were evaluated. METHODS: FIRST STUDY: 36 cirrhotic patients were studied at baseline and 30 and 60 minutes after a standard meal and then treated with propranolol (139 +/- 9 mg/d during 39 +/- 2 days). SECOND STUDY: After baseline measurements, patients were randomized into 3 groups: (1) placebo, (2) octreotide (100 microg), or (3) octreotide (200 microg) (n = 12 for each group). Thirty minutes postinjection a new baseline was established and measurements were repeated 30 and 60 minutes after the meal. RESULTS: First study: Baseline portal pressure was 18.1 +/- 1.2 mm Hg, 30 and 60 minutes after the meal it was 21.5 +/- 0.8 mm Hg and 20.5 +/- 0.8 mm Hg, respectively (both P < 0.01 vs. baseline). Cardiac index (CI) was 4.5 +/- 0.2, 4.8 +/- 0.2, and 4.9 +/- 0.2 L x min(-1) x m(-2), respectively (both P < 0.05 vs. baseline). Peripheral vascular resistance was 1012 +/- 56, 902 +/- 51 (P = NS), and 884 +/- 49 dynes x sec x cm(-5) (P< 0.05 vs. baseline), respectively. Second study: Propranolol and placebo did not blunt postprandial increase in portal pressure. Octreotide (100 microg) partially ameliorated postprandial increase in portal pressure. Octreotide (200 microg) significantly enhanced the portal hypotensive effect of propranolol and blunted the postprandial increase in portal pressure. CONCLUSIONS: Octreotide blunts postprandial increase in portal pressure not prevented by long-term propranolol administration.