Effect of Surfactant on Ventilation-induced Mediator Release in Isolated Perfused Mouse Lungs

doi:10.1006/pupt.2002.0383

Pulmonary Pharmacology & Therapeutics

Volume 15, Issue 5, October 2002, Pages 455-461

https://doi.org/10.1006/pupt.2002.0383 Get rights and content

Abstract

The human acute respiratory distress syndrome (ARDS) is a severe pulmonary complication with high mortality rates. To support their vital functions, patients suffering from ARDS are mechanically ventilated. Recently it was shown that low tidal volume ventilation reduces mortality and pro-inflammatory mediator release in these patients, suggesting biotrauma as a side effect of mechanical ventilation. Because the application of exogenous surfactant has been proposed as a treatment for ARDS, we investigated the effect of surfactant on ventilation-induced release of tumor necrosis factor (TNF), interleukin-6 (IL-6) and 6-keto-PGF_1α (the stable metabolite of prostacyclin) in isolated perfused mouse lungs ventilated with high end-inspiratory pressures. Instillation of 100 mg/kg surfactant into the lungs was well tolerated and improved tidal volume, pulmonary compliance and alveolar expansion. Exogenous surfactant increased the ventilation-induced liberation of TNF and IL-6 into the perfusate, but had no effect on the release of 6-keto-PGF_1α. The surfactant preparation used reduced baseline TNF production by murine alveolar macrophages, indicating that the exaggeration of ventilation-induced TNF release cannot be explained by a direct effect of surfactant on these cells. We hypothesize that ventilation-induced mediator release is explained by stretching of lung cells, which is reinforced by surfactant. The findings that in this model of ventilation-induced lung injury exogenous surfactant at the same time improved lung functions and enhanced mediator release suggest that surfactant treatment may prevent barotrauma and augment biotrauma.

References (36)

AS Slutsky
Lung injury caused by mechanical ventilation
Chest
(1999)
RG Spragg
Surfactant replacement therapy
Clin Chest Med
(2000)
A Bhagyalakshmi et al.
Mechanism of shear-induced prostacyclin production in endothelial cells
Biochem Biophys Res Commun
(1989)
H Yamamoto et al.
Stretch induces a growth factor in alveolar cells via protein kinase
Respir Physiol
(2001)
GR Bernard et al.
The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination
Am J Respir Crit Care Med
(1994)
MBP Amato et al.
Beneficial effects of the ‘open lung approach’ with low distending pressures in acute respiratory distress syndrome
Am J Respir Crit Care Med
(1995)
MB Amato et al.
Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome
N Engl J Med
(1998)
VM Ranieri et al.
Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. A randomized controlled trial
JAMA
(1999)
N Engl J Med
(2000)
D Dreyfuss et al.
Ventilator-induced lung injury. Lessons from experimental studies
Am J Respir Crit Care Med
(1998)

LN Tremblay et al.

Ventilator-induced injury: from barotrauma to biotrauma

Proc Assoc Am Physicians

(1998)

H-D Held et al.

Ventilation-induced chemokine and cytokine release is associated with activation of NF-κB and is blocked by steroids

Am J Respir Crit Care Med

(2001)

CC Dos Santos et al.

Mechanisms of ventilator-induced lung injury: a perspective

J Appl Physiol

(2000)

S Uhlig et al.

Molecular mechanisms of pro-inflammatory responses in overventilated lungs

Recent Res Devel Resp Crit Care Med

(2001)

AN von Bethmann et al.

Prolonged hyperventilation is required for release of tumor necrosis factor-α but not IL-6

Appl Cardiopulm Pathol

(1996)

AN von Bethmann et al.

Hyperventilation induces release of cytokines from perfused mouse lung

Am J Respir Crit Care Med

(1998)

J Pugin et al.

Activation of human macrophages by mechanical ventilation in vitro

Am J Physiol

(1998)

NE Vlahakis et al.

Stretch induces cytokine release by alveolar epithelial cells in vitro

Am J Physiol

(1999)

Cited by (34)

The administration of surfactant decreased oxidative stress in lungs of mice exposed to cigarette smoke
2018, International Immunopharmacology
Citation Excerpt :
These findings corroborate with the data from the literature where no anti-inflammatory effects of exogenous surfactant were observed [44,49]. In 2002, Stamme et al. using an isolated model of ventilated murine lungs, demonstrated that exogenous surfactant is able to increase the release of inflammatory cytokines through direct leukocyte action and indirectly through excessive alveoli distention [50]. One of the hypotheses for this inflammatory response is that it may be related to a period of adaptation of the organism to the presence of foreign proteins present in the porcine surfactant and to the mechanical effects of the instillation process that can release cytokines such as TNF and IL-1β and cause adhesion of leukocytes to the vascular endothelium [44].
The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and proteins, has immunomodulatory action. This study aimed to evaluate the effects of exogenous surfactant on pulmonary inflammatory response in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided into four groups: control group exposed to ambient air (CG); surfactant treated group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day and SG and CSSG received the surfactant by intranasal instillation. At the end of the experiment, the animals were euthanatized for the collection of bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in BALF increased in CSG compared to CG, however, there was a decrease in CSSG compared to CSG. There was an increase in lipid peroxidation in SG and CSG compared to CG while there was a decrease in CSSG compared to CSG. Regarding the antioxidant enzymes, the catalase (CAT) activity increased in all groups compared to CG and the superoxide dismutase (SOD) activity decreased in CSG compared to the CG and SG. There was an increase in TNF in SG, CSG and CSSG compared to CG. There was an increase in IL-17 in CSSG compared to CG. There was an increase in CCL5 in SG and CSSG compared to CG. Therefore, our results demonstrated that the administration of exogenous surfactant was able to decrease the oxidative processes in the lungs of mice induced by short-term exposure to CS.
Exogenous surfactant attenuation of ischemia-reperfusion injury in the lung through alteration of inflammatory and apoptotic factors
2009, Journal of Thoracic and Cardiovascular Surgery
Lung ischemia–reperfusion injury is associated with impaired gas exchange from increased edema formation and surfactant inactivation. Surfactant replacement therapy is believed to improve gas exchange and lung function, but its effect on inflammation is less well understood. We therefore examined the effects of exogenous surfactant on inflammatory and apoptotic factors in the lung in a rat model of lung ischemia–reperfusion injury.
The left lung in rats was subjected to ischemia for 120 minutes and reperfusion for as long as 240 minutes. Sham-treated animals underwent sham surgery and mechanical ventilation for equivalent times. Rats received porcine surfactant or saline solution intratracheally either before or just after ischemia. Lungs were analyzed histopathologically and for expressions of inducible nitric oxide, cytokines, and caspase-3.
Lung ischemia–reperfusion injury resulted in worse lung histopathologic characteristics than in sham-operation animals. At 2 hours of reperfusion, lung ischemia–reperfusion injury animals showed increased pulmonary caspase-3 expression. Moreover, lung ischemia–reperfusion injury resulted in inducible nitric oxide expression at all time points. Exogenous surfactant resulted in less inflammatory cell infiltration and edema in the lungs relative to saline-treated animals. Surfactant decreased activated caspase-3 expression and increased inducible nitric oxide expression relative to saline-treated animals. At 4 hours of reperfusion, surfactant increased interleukin 6 and 10 expressions in the lung.
This study showed a significant improvement in lung histologic characteristics after surfactant therapy, accompanied by reduced apoptosis and increased anti-inflammatory cytokine levels. Interestingly, surfactant therapy also increased pulmonary inducible nitric oxide expression.
Pathogenetic significance of biological markers of ventilator-associated lung injury in experimental and clinical studies
2006, Chest
For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis.
Pharmacological interventions in ventilator-induced lung injury
2004, Trends in Pharmacological Sciences
During mechanical ventilation the lungs are exposed to substantial physical forces. This is particularly true for patients with acute lung injury, where the applied pressures are two to three times higher than those present during normal breathing. The resultant overdistension activates specific mechanotransduction pathways, many of which activate inflammation pathways that might lead to (further) acute lung injury. In this article, we review evidence suggesting that pharmacological strategies can interfere with ventilator-induced lung injury at different stages of the inflammatory cascade: blockade of transcription factors, neutralization of chemokines, cytokines and neuropeptides, and inhibition of proteases. These findings provide rationale for the use of anti-inflammatory therapies to treat the side-effects of mechanical ventilation.
The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence
2022, Inflammopharmacology
Surfactant dysfunction and alveolar collapse are linked with fibrotic septal wall remodeling in the TGF-β1-induced mouse model of pulmonary fibrosis
2019, Laboratory Investigation

View all citing articles on Scopus

^f1: Author for correspondence: Stefan Uhlig, Division Pulmonary Pharmacology, Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany. Tel.: +49-4537-188478, Fax: +49-4537-188778. E-mail: [email protected]

View full text

Regular ArticleEffect of Surfactant on Ventilation-induced Mediator Release in Isolated Perfused Mouse Lungs

Abstract

Chest

Clin Chest Med

Biochem Biophys Res Commun

Respir Physiol

The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination

Am J Respir Crit Care Med

Beneficial effects of the ‘open lung approach’ with low distending pressures in acute respiratory distress syndrome

Am J Respir Crit Care Med

Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome

N Engl J Med

Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. A randomized controlled trial

JAMA

N Engl J Med

Ventilator-induced lung injury. Lessons from experimental studies

Am J Respir Crit Care Med

Ventilator-induced injury: from barotrauma to biotrauma

Proc Assoc Am Physicians

Ventilation-induced chemokine and cytokine release is associated with activation of NF-κB and is blocked by steroids

Am J Respir Crit Care Med

Mechanisms of ventilator-induced lung injury: a perspective

J Appl Physiol

Molecular mechanisms of pro-inflammatory responses in overventilated lungs

Recent Res Devel Resp Crit Care Med

Prolonged hyperventilation is required for release of tumor necrosis factor-α but not IL-6

Appl Cardiopulm Pathol

Hyperventilation induces release of cytokines from perfused mouse lung

Am J Respir Crit Care Med

Activation of human macrophages by mechanical ventilation in vitro

Am J Physiol

Stretch induces cytokine release by alveolar epithelial cells in vitro

Am J Physiol

Regular Article
Effect of Surfactant on Ventilation-induced Mediator Release in Isolated Perfused Mouse Lungs