Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model
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.
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 (IκBα), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL6) gene expression in the lungs and TNF-α and IL-6 protein serum concentrations were analyzed.
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 IκBα, and a higher lung expression and serum concentrations of pro-inflammatory cytokines.
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.
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- Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- March 2010
- Online ISSN
- BioMed Central
- Additional Links
- Author Affiliations
- 1. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain
- 2. Multidisciplinary Organ Dysfunction Evaluation Research Network (MODERN), Research Unit, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
- 3. Keenan Research Center at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada
- 4. Research Unit, Hospital Universitario N.S. de Candelaria, Tenerife, Spain
- 5. Department of Anatomy, Pathology & Histology, University of La Laguna, Tenerife, Spain
- 6. Department of Clinical Biochemistry, Hospital Universitario NS de Candelaria, Tenerife, Spain
- 7. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
- 8. King Saud University, Riyadh, Saudi Arabia
- 10. Department of Anesthesia, Harvard Medical School, Boston, MA, USA
- 9. Department of Respiratory Care, Massachusetts General Hospital, Boston, Massachusetts, USA