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Respiratory Research
Published in: Respiratory Research 1/2009

Open Access 01-12-2009 | Research

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

Authors: Laurent Savale, Ly Tu, Dominique Rideau, Mohamed Izziki, Bernard Maitre, Serge Adnot, Saadia Eddahibi

Published in: Respiratory Research | Issue 1/2009

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Abstract

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.
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Metadata
Title
Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice
Authors
Laurent Savale
Ly Tu
Dominique Rideau
Mohamed Izziki
Bernard Maitre
Serge Adnot
Saadia Eddahibi
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2009
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-10-6

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