Effect of Il-1 Blockade on Inflammatory Manifestations of Acute Ventilator-Induced Lung Injury in a Rabbit Model

Narimanbekov, I O; Rozycki, Henry J.

doi:10.3109/01902149509068830

Cited by 122 publications

(49 citation statements)

References 28 publications

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“…Antibody blockade of TNF-α decreased histopathologic lung injury in surfactant-depleted rats, 13 while blockade of IL-1 with IL-1Ra attenuated lung injury after 8 h of ventilation in surfactant-depleted rabbits. 24 These data suggest a pathogenetic role for TNF-α and IL-1 in VALI. In preterm lambs, higher lung volume ventilation with high PEEP resulted in greater increases in IL-1β, IL-6, and IL-8 but not TNF-α.…”

Section: Cytokines and Chemokines In Experimental Studiesmentioning

confidence: 82%

Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

Frank

Parsons

Matthay

2006

Chest

116

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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. Keywords ARDS; critical care; ventilation; ventilator-induced lung injuryAlthough clinicians and researchers have been interested in ventilator-induced lung injury (VILI) for at least 30 years, the reduction in mortality associated with low tidal volume ventilation in patients with acute lung injury (ALI) and ARDS 1 has directed increasing scientific interest toward the mechanisms of VILI. One of the greatest difficulties in clinical studies has been distinguishing the underlying lung injury responsible for the patient's respiratory failure from the lung injury resulting from the particular settings of the mechanical ventilator. Consequently, investigators have searched for biological markers that will reflect ventilator-attributable lung injury. The term VILI generally refers to experimental models in which lung injury in induced directly by an injurious ventilation strategy. Ventilator-associated lung injury (VALI) refers to the additional injury imposed on a previously injured lung by mechanical ventilation in either the clinical setting or in experimental studies. For the purposes of this review, the term ventilator-attributable injury encompasses all of these types of injury. Researchers have used a variety of experimental models to determine the effects of mechanical ventilation or mechanical strain on the expression of biological markers of inflammation or Biologic Markers of Inflammation in Clinical StudiesThe role of the innate immune response and inflammation in the pathogenesis of VILI has been widely studied in recent years. Although some have suggested that inflammation may not be integral to the initiation of VILI, clearly a preponderance of data in this field support a major pathogenetic role for inflammation and lung neutrophil recruitment. The majority of biological markers identified in plasma, serum, pulmonary edema fluid, and BAL fluid in experimental studies are cytokines and chemokines. Although none of these mediator...

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Section: Cytokines and Chemokines In Experimental Studiesmentioning

confidence: 82%

Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

Frank

Parsons

Matthay

2006

Chest

116

View full text Add to dashboard Cite

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“…Chemical and biological inhibition of the IL-1 pathway has improved indices of VILI in animal models (28,29), but most patients with ARDS did not benefit from IL-1 receptor antagonist treatment (30). Inflammasome-mediated IL-1b secretion has been implicated in the pathology of lung inflammation (31), but its relationship to IL-18 is not known.…”

Section: Discussionmentioning

confidence: 99%

Inflammasome-regulated Cytokines Are Critical Mediators of Acute Lung Injury

Dolinay

Kim

Howrylak

et al. 2012

Am J Respir Crit Care Med

483

424

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Rationale: Despite advances in clinical management, there are currently no reliable diagnostic and therapeutic targets for acute respiratory distress syndrome (ARDS). The inflammasome/caspase-1 pathway regulates the maturation and secretion of proinflammatory cytokines (e.g., IL-18). IL-18 is associated with injury in animal models of systemic inflammation. Objectives: We sought to determine the contribution of the inflammasome pathway in experimental acute lung injury and human ARDS. Methods: We performed comprehensive gene expression profiling on peripheral blood from patients with critical illness. Gene expression changes were assessed using real-time polymerase chain reaction, and IL-18 levels were measured in the plasma of the critically ill patients. Wild-type mice or mice genetically deficient in IL-18 or caspase-1 were mechanically ventilated using moderate tidal volume (12 ml/kg). Lung injury parameters were assessed in lung tissue, serum, and bronchoalveolar lavage fluid. Measurements and Main Results: In mice, mechanical ventilation enhanced IL-18 levels in the lung, serum, and bronchoalveolar lavage fluid. IL-18-neutralizing antibody treatment, or genetic deletion of IL-18 or caspase-1, reduced lung injury in response to mechanical ventilation. In human patients with ARDS, inflammasome-related mRNA transcripts (CASP1, IL1B, and IL18) were increased in peripheral blood. In samples from four clinical centers, IL-18 was elevated in the plasma of patients with ARDS (sepsis or trauma-induced ARDS) and served as a novel biomarker of intensive care unit morbidity and mortality. Conclusions: The inflammasome pathway and its downstream cytokines play critical roles in ARDS development.

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“…Fixed samples were embedded in paraffin, sectioned at 6 m, and stained with hematoxylin and eosin. A pathologist evaluated the changes in lung histology by using a scoring system, modified from a previously described method (9), which used coded samples so that the reviewer had no knowledge of the treatment group. Twenty-four areas of lung parenchyma in each animal were observed at a 10× objective magnification and were graded on a scale of 0 to 4 (0: absent, appears normal, 1: light, 2: moderate, 3: strong, and 4: intense) for congestion, edema, inflammation, and hemorrhage.…”

Section: Lung Histologymentioning

confidence: 99%

Cepharanthin, an Alkaloid From Stephania Cepharantha, Inhibits Increased Pulmonary Vascular Permeability in an Ovine Model of Sepsis

Murakami¹,

Cox²,

Hawkins³

et al. 2003

Shock

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Sepsis is a life-threatening event when it occurs in patients suffering from smoke inhalation injury. Pneumonia is one of the most frequent sources of infection in sepsis. Activated leukocytes likely play a role in the pathogenesis of sepsis. Cepharanthin is a biscoclaurine alkaloid that reportedly inhibits the activation of neutrophils. In this study, we investigated the effects of cephranthin on a post-smoke inhalation model of sepsis in sheep. Female sheep (n = 15) were surgically prepared for the study. After 5 days recovery from the operative procedures, tracheostomy was performed in all animals and 48 breaths of cotton smoke (<40 degrees C) were given via a modified bee smoker under halothane anesthesia. After smoke insufflation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was instilled into the airway using a bronchoscope. All of the animals were mechanically ventilated with 100% O(2). Cepharanthin (1.3 mg/kg/h) was infused in five sheep continuously beginning 1 h after the insult and thereafter for the remainder of the 24-h study period. Control animals (n = 6) were treated with 5% dextrose as a vehicle control. Cepharanthin significantly attenuated changes in lung histology as well as in lung wet/dry weight ratio. An in vitro study revealed that cepharanthin inhibited the release of neutrophil elastase from isolated neutrophils stimulated with either formyl-methyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate with an IC(50) of 60 microM. Cepharanthin also inhibited the fMLP-induced increase in intracellular calcium levels of neutrophils. This result indicates cepharanthin inhibits protein kinase C or a more downstream signaling pathway in neutrophil activation. In conclusion, cepharanthin attenuates acute lung injury and septic shock after smoke inhalation in sheep.

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Effect of Il-1 Blockade on Inflammatory Manifestations of Acute Ventilator-Induced Lung Injury in a Rabbit Model

Cited by 122 publications

References 28 publications

Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

Inflammasome-regulated Cytokines Are Critical Mediators of Acute Lung Injury

Cepharanthin, an Alkaloid From Stephania Cepharantha, Inhibits Increased Pulmonary Vascular Permeability in an Ovine Model of Sepsis

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