Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

Respir Res. 2009 Jan 27;10(1):6. doi: 10.1186/1465-9921-10-6.


Background: Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6).

Methods: To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/-) and wild-type (IL-6+/+) mice exposed to hypoxia for 2 weeks.

Results: Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer) mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs) and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines.

Conclusion: These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cytokine Receptor gp130 / metabolism
  • Disease Models, Animal
  • Humans
  • Hypertension, Pulmonary / immunology*
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / physiopathology
  • Hypertrophy, Right Ventricular / immunology
  • Hypoxia / complications
  • Hypoxia / immunology*
  • Hypoxia / physiopathology
  • Interleukin-6 / deficiency
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lung / immunology
  • Lung / pathology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / immunology
  • Muscle, Smooth, Vascular / pathology
  • Pneumonia / immunology*
  • Pneumonia / physiopathology
  • Pulmonary Artery / immunology
  • Pulmonary Artery / pathology
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-6 / metabolism
  • Time Factors


  • IL6 protein, human
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130