Contribution of inflammation to the pathology of idiopathic pulmonary arterial hypertension in children.

Idiopathic pulmonary arterial hypertension (IPAH) is an incurable disease of multifactorial origin. Inflammation is frequently observed in IPAH, but its role in the pathobiology is unclear. In this study the distribution, nature and number of inflammatory cells in periarterial infiltrates in lungs of children with IPAH, pulmonary arterial hypertension associated with congenital heart disease (APAH) and in normal lung tissue were characterised and compared using immunohistochemistry The influence of treatment with combined prostacyclin and endothelin receptor blockers was also studied. In children with IPAH, both treated and untreated, but not in children with APAH or normal children, extensive periarterial infiltrates were present comprising macrophages and T lymphocytes with S100A4- and bone morphogenetic protein receptor type-2 (BMPR2)-positive cells. Although rarely co-expressing macrophage-specific antigens, BMPR2-positive cells were frequently closely associated with macrophages and lymphocytes. They were more abundant around peripheral arteries of children with IPAH than in APAH or normal lungs (15.1 (3.5), 2.3 (0.9) and 2.3 (0.9) cells/mm external elastic lamina, respectively; p<0.01 for IPAH vs APAH or normal lungs). Prostacyclin with endothelin receptor blockade resulted in a significant reduction in endothelial cell activation as indicated by human leucocyte antigen (HLA)-DR expression (treated 17% vs untreated 100%, p<0.002). This study shows that pulmonary inflammation is present in the lungs of children with IPAH. This may indicate a role for inflammation in the pathobiology of IPAH and provide the rationale for novel therapeutic intervention.