Inflammatory cytokines in pulmonary hypertension

Abstract

Pulmonary hypertension is an "umbrella term" used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension.This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension.

Figure 1

Plexiform lesion in a patient with PAH. Complex vascular lesion with perivascular fibrosis and infiltration by lymphocytes, plasma cells (arrow head) and eosinophils (*). HE staining.

Figure 2

Proposed mechanism of BMPR2 downregulation by IL-6. The binding of IL-6 to its receptor triggers the phosphorylation of STAT3. Phosphorylated STAT3 forms a dimer and translocates into the nucleus, where it activates the transcription of the miR-17/92 cluster. The mature miRNA transfers into the cytoplasma and, by binding to the target mRNA, silences BMPR2.