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The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

Puntorieri V, Hiansen JQ, McCaig LA, Yao LJ, Veldhuizen RA, Lewis JF - BMC Pulm Med (2013)

Bottom Line: Instillation of exogenous surfactant did not influence the development of lung injury.Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology & Pharmacology, Western University, London, Ontario, Canada. vpuntori@uwo.ca.

ABSTRACT

Background: Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.

Methods: Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).

Results: For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.

Conclusions: The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

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Experiment 2: IL-6 levels measured in lung perfusate at 0, 30, 60, 90, 120 min. Data are expressed as mean ± SEM. *p < 0.05 versus respective Air control at each time point; n = 6 per group.
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Figure 5: Experiment 2: IL-6 levels measured in lung perfusate at 0, 30, 60, 90, 120 min. Data are expressed as mean ± SEM. *p < 0.05 versus respective Air control at each time point; n = 6 per group.

Mentions: To test the hypothesis of a role for exogenous surfactant in down-modulating systemic inflammation in ALI, sequential lung perfusate samples, as a surrogate for systemic inflammation, were analyzed for IL-6 concentrations. As shown in Figure 5, there were significantly higher levels of IL-6 in the perfusate of acid-instilled mice compared to the respective air-instilled controls at every time point (0, 30, 60, 90, 120 min; Acid No Treatment vs Air No Treatment; Acid bLES vs Air bLES). Perfusate IL-6 levels were not significantly affected by exogenous surfactant administration, with no differences between Air bLES and Air No Treatment and no change between Acid bLES and Acid No treatment.


The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

Puntorieri V, Hiansen JQ, McCaig LA, Yao LJ, Veldhuizen RA, Lewis JF - BMC Pulm Med (2013)

Experiment 2: IL-6 levels measured in lung perfusate at 0, 30, 60, 90, 120 min. Data are expressed as mean ± SEM. *p < 0.05 versus respective Air control at each time point; n = 6 per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222563&req=5

Figure 5: Experiment 2: IL-6 levels measured in lung perfusate at 0, 30, 60, 90, 120 min. Data are expressed as mean ± SEM. *p < 0.05 versus respective Air control at each time point; n = 6 per group.
Mentions: To test the hypothesis of a role for exogenous surfactant in down-modulating systemic inflammation in ALI, sequential lung perfusate samples, as a surrogate for systemic inflammation, were analyzed for IL-6 concentrations. As shown in Figure 5, there were significantly higher levels of IL-6 in the perfusate of acid-instilled mice compared to the respective air-instilled controls at every time point (0, 30, 60, 90, 120 min; Acid No Treatment vs Air No Treatment; Acid bLES vs Air bLES). Perfusate IL-6 levels were not significantly affected by exogenous surfactant administration, with no differences between Air bLES and Air No Treatment and no change between Acid bLES and Acid No treatment.

Bottom Line: Instillation of exogenous surfactant did not influence the development of lung injury.Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology & Pharmacology, Western University, London, Ontario, Canada. vpuntori@uwo.ca.

ABSTRACT

Background: Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.

Methods: Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).

Results: For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.

Conclusions: The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

Show MeSH
Related in: MedlinePlus