Abstract
Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean±standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40±0.33 versus [vs] 2.40±0.55, p = 0.007), along with greater bacterial concentrations (6.13±0.63 vs. 4.96±1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-αserum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-α: 1656±166 vs. 1005±89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression.
Highlights
Mechanical ventilation (MV) is sometimes the only way to care for critically ill patients with respiratory failure, many adverse effects, including ventilator-associated pneumonia (VAP), are common [1, 2]
Mechanical ventilation worsens lung damage and impairs bacterial lung clearance We developed an animal model of S. aureus Ventilator-associated pneumonia (VAP) in lungs previously subjected to mechanical ventilation (MV)
These findings suggest that lung damage was more severe and earlier in animals subjected to MV and pneumonia than in spontaneously breathing (SB) animals with pneumonia
Summary
Mechanical ventilation (MV) is sometimes the only way to care for critically ill patients with respiratory failure, many adverse effects, including ventilator-associated pneumonia (VAP), are common [1, 2]. Mechanical Ventilation and Lung Response to S. aureus ventilator-days) [3]. A rapid immune lung response is necessary to ensure microbial clearance. In the airways, both bronchial and alveolar epithelial cells take part in the host innate immune response, mainly through their ability to produce inflammatory mediators [4]. It is clearly recognized that innate immunity is activated through pattern recognition receptor-related pathways [5]. TLRs can recognize a wide range of pathogen-associated microbial patterns and generate inflammatory signals to modulate innate immune responses [6]. TLR2 expression seems to be sensitive to mechanical stress, as shown in the endothelium [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
