Primary pulmonary hypertension (PPH) is characterized by the proliferation of smooth-muscle cells, fibroblasts, and endothelial cells in the walls of small pulmonary arteries. In order to evaluate a role for proinflammatory cytokines in this process, we studied the concentration of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the serum of 29 patients with severe PPH referred to our center for lung transplantation. Results were compared with those obtained in 15 normal controls and nine patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD-PH). TNF alpha serum levels were within the normal range in each group. This contrasted with increased IL-1 beta serum levels in severe PPH (118 +/- 36 pg/ml, mean +/- SEM) as compared with controls (3 +/- 1 pg/ml, p < 0.001) or COPD-PH patients (3 +/- 1 pg/ml, p < 0.001). IL-6 serum concentrations were also higher in severe PPH (66 +/- 20 pg/ml) than in controls (14 +/- 6 pg/ml, p < 0.01). This study demonstrates increased serum levels of IL-1 beta and IL-6 in severe PPH, and suggests a role for proinflammatory cytokines in PPH.

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aaThis review focuses on the pulmonary vascular complications of chronic liver failure and portal hypertension. The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome (HPS), which is characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance (PVR) is elevated. The exact pathophysiological mechanisms of these pulmonary vascular disorders are unknown. However, since HPS and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the factor that determines their development must be portal hypertension.A brief review of the haemodynamic changes observed in cirrhosis with portal hypertension is summarized, and the clinical and experimental evidence suggesting that the liver exerts a critical influence on the regulation of pulmonary vascular tone and angiogenesis is described. Portopulmonary hypertension is then discussed, focusing in turn on its clinical presentations, management and potential mechanisms, and referring to our findings in 39 patients with portopulmonary hypertension and 140 patients with primary pulmonary hypertension (PPH) admitted between 1986 and 1996 at Antoine Béclère Hospital. Finally, HPS will be examined, with a discussion of the mechanisms of hypoxaemia and intrapulmonary vascular dilatation, as well as its clinical presentation, diagnosis and treatment, with special attention to liver transplantation. Haemodynamics in cirrhosis with portal hypertensionAn understanding of pulmonary haemodynamics in liver disease with portal hypertension is important to a study of the pulmonary vascular disorders seen in this setting. A hyperdynamic circulatory state with high cardiac output, low systemic vascular resistance and low PVR is present in 30-50% of patients with cirrhosis and also in animal models of portal hypertension [1][2][3][4]. Compared with healthy subjects ( fig. 1) The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance is elevated. Since hepatopulmonary syndrome and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the common factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in the hepatopulmonary syndrome and haemodynamic failure in portopulmonary hypertension. The severity of hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome is common after liver transplantation, which has an uncertain effect in portopulmonary hypertension. The pathoph...