Comprehensive analysis of inflammatory markers in chronic thromboembolic pulmonary hypertension patients

Eur Respir J. 2014 Oct;44(4):951-62. doi: 10.1183/09031936.00145013. Epub 2014 Jul 17.

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with chronic inflammation but the pathological mechanisms are largely unknown. Our study aimed to simultaneously profile a broad range of cytokines in the supernatant of pulmonary endarterectomy (PEA) surgical material, as well as prospectively in patients with CTEPH to investigate whether circulating cytokines are associated with haemodynamic and physical characteristics of CTEPH patients. Herein, we show that PEA specimens revealed a significant upregulation of interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-γ-induced protein-10 (IP)-10, macrophage inflammatory protein (MIP)1α and RANTES compared to lung tissue from healthy controls. In prospectively collected serum, levels of IL-6, IL-8, IP-10, monokine induced by interferon-γ (MIG) and MIP1α were significantly elevated in CTEPH patients compared to age- and sex-matched healthy controls. In serum of idiopathic pulmonary arterial hypertension (IPAH) patients, only IP-10 and MIG were significantly increased. In CTEPH but not in IPAH, IP-10 was negatively correlated with cardiac index, 6-min walking distance and carbon monoxide diffusion capacity. In vitro, IP-10 significantly increased migration of freshly isolated adventitial fibroblasts. Our study is the first to show that IP-10 secretion is associated with poor pulmonary haemodynamics and physical capacity in CTEPH and might be involved in the pathological mechanism of PEA tissue formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Chronic Disease
  • Cytokines / blood*
  • Female
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / etiology
  • Inflammation / blood*
  • Inflammation / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Embolism / blood*
  • Pulmonary Embolism / complications

Substances

  • Biomarkers
  • Cytokines