Patients with pulmonary hypertension related to congenital systemic-to-pulmonary shunts are characterized by inflammation involving endothelial cell activation and platelet-mediated inflammation.

Objective. We examined inflammatory mediators in patients with pulmonary hypertension related to congenital systemic-to-pulmonary shunts and the change in these markers during treatment with bosentan. Background. Inflammatory mechanisms probably play a pathogenic role in idiopathic pulmonary arterial hypertension. Their involvement in pulmonary hypertension related to congenital systemic-to-pulmonary shunts is largely unknown. Patients and Methods. Plasma levels of several inflammatory mediators were determined by enzyme immunoassays in 14 children and adolescents with pulmonary hypertension related to congenital systemic-to-pulmonary shunts before and after 12 months treatment with bosentan, and compared with levels in 54 healthy controls. Results. The patients were characterized by increased plasma levels of von Willebrand factor (similar to 2.5-fold), C-reactive protein (similar to 3.5-fold), and soluble CD40 ligand (similar to 2.5-fold) as compared with controls, representing markers of endothelial cell activation, systemic inflammation, and platelet-mediated inflammation, respectively. Patients also had significantly elevated plasma levels of osteoprotegerin (similar to 1.6-fold). Within the study group, N-terminal probrain natriuretic peptide levels correlated significantly with the concentrations of C-reactive protein (r = 0.61, P < .027) and von Willebrand factor (r = 0.74, P = .004). Except for a decline in monocyte chemoattractant protein-1 and receptor activator of nuclear factor-kappa B ligand, bosentan therapy did not attenuate the systemic inflammation. Conclusion. Children and adolescents with pulmonary hypertension related to congenital systemic-to-pulmonary shunts are characterized by enhanced systemic inflammation involving increased endothelial cell activation and platelet-mediated inflammation. These inflammatory responses seem essentially to be unmodified by bosentan, potentially representing new targets for therapy in this disorder.