Format

Send to

Choose Destination
Respir Res. 2010 Mar 3;11:27. doi: 10.1186/1465-9921-11-27.

Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model.

Author information

1
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain. jesus.villar54@gmail.com

Abstract

BACKGROUND:

Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury.

METHODS:

Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (VT) (20 ml/kg) and low VT (6 ml/kg). Histological evaluation, TLR2, TLR4, IRAK3 gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (IkappaBalpha), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) gene expression in the lungs and TNF-alpha and IL-6 protein serum concentrations were analyzed.

RESULTS:

High VT mechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of IRAK3 lung gene expression and protein levels, a significant decrease of IkappaBalpha, and a higher lung expression and serum concentrations of pro-inflammatory cytokines.

CONCLUSIONS:

The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections.

PMID:
20199666
PMCID:
PMC2841148
DOI:
10.1186/1465-9921-11-27
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center