Cytokine Balance in the Lungs of Patients with Acute Respiratory Distress Syndrome

Park, William Y.; Goodman, Richard B.; Steinberg, Kenneth P.; Ruzinski, John; Radella, Frank; Park, David R.; Pugin, Jérôme; Skerrett, Shawn J.; Hudson, Leonard D.; Martin, Thomas R.

doi:10.1164/ajrccm.164.10.2104013

Cited by 494 publications

(401 citation statements)

References 43 publications

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“…Cytokines involved in the early phase of inflammatory response include IL1, IL2, IL6 and IL8 (27)(28)(29)(30)(31). Some of these cytokines are produced in the lung by local resident cells such as alveolar macrophages, lung epithelial cells and fibroblasts or by cells such as neutrophils, lymphocytes, monocytes and platelets as a response to local or systemic injury (5,27,(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

“…There are few studies addressing cytokine levels after esophageal resection itself. To date, most studies deal with the comparison of cytokine levels between at-risk patients for lung injury and such which had developed ALI or even ARDS in the course of their disease in order to find cytokines which predict the development of lung injury and outcome (5,45,46).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence from several studies indicates that a complex network of inflammatory cytokines and chemokines has a leading role in mediation, amplification and perpetuation of the process of lung injury (5).…”

Section: Introductionmentioning

confidence: 99%

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Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy

Frick

Justinger²,

Rubie³

et al. 2011

Oncol Rep

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Abstract. Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS. In this trial, the cytokine levels of IL6, IL8 and IL10 were measured and compared in 30 patients who had undergone an extended radical thoracoabdominal esophagectomy for esophageal cancer, via anterolateral thoracotomy (n=17) or posterolateral thoracotomy (n=13). Patients of both groups were similar in terms of age, sex and preoperative pulmonary function as well as in the anesthetic procedures they have undergone. All patients displayed significantly increased serum levels of IL6 and IL8 after thoracoabdominal esophagectomy. However, patients who were subjected to an anterolateral thoracotomy were reported with significantly higher serum levels of IL6 and IL8 compared to patients who had received a posterolateral thoracotomy. Thus, the choice of the thoracotomy method during the thoracoabdominal esophagectomy and the resultant cytokine levels may contribute to the occurrence of postoperative pulmonary complications and may have an impact on the extent and severity of the surgical stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy

Frick

Justinger²,

Rubie³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

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“…These proteins included TNF-a, IL-1b, IL-6, LBP, and p38 MAPK. Previous studies showed that TNF-a, IL-1b, IL-6, and LBP are present in the BALF of patients with ARDS and contribute to the pro-inflammatory environment (16)(17)(18)(19)(20). In addition, p38 MAPK has also been shown to regulate key physiologic responses, including neutrophil recruitment and clearance of edema fluid, during the development of lung injury (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Chang¹,

Hayashi²,

Gharib³

et al. 2008

Am J Respir Crit Care Med

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Rationale: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. Objectives: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Methods: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n 5 7), 3 (n 5 8), and 7 (n 5 5) of ARDS were compared with findings in normal volunteers (n 5 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. Measurements and Main Results: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Conclusions: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

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“…Unlike PBEF, IL-6 is a well recognized ALI candidate gene and ALI biomarker. The elevation and persistence of circulating IL-6 has been associated with increased mortality in critically ill patients with ARDS, sepsis, and trauma, and IL-6 concentrations have been shown to be elevated in the BAL fluid from patients with established severe ALI (38,39). Functional polymorphisms in the promoter region of the IL-6 gene exist (G174C) with the C allele associated with reduced gene promoter activity, lower circulating IL-6 concentrations, and a lower mortality rate in patients with acute respiratory failure admitted to the ICU (9).…”

Section: Preliminary Il-6 Gene Variant Genotyping In Alimentioning

confidence: 99%

Functional Genomic Insights into Acute Lung Injury: Role of Ventilators and Mechanical Stress

Nonas

Finigan

Gao

et al. 2005

Proceedings of the American Thoracic Society

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Acute lung injury (ALI) is a complex and devastating illness, often occurring in the setting of sepsis and trauma. Despite recent advances in the understanding and treatment of ALI, pathogenic mechanisms and genetic modifiers in ALI remain incompletely understood. Furthermore, there has been increasing interest in the identification of genetic variations that contribute to ALI susceptibility and severity in order to gain unique insights into ALI pathogenesis and to design novel treatment strategies. However, the sporadic nature of ALI and the lack of family-based cohort studies preclude conventional genomic approaches such as linkage mapping (or "positional cloning"). We have used a "candidate gene approach" with extensive gene expression profiling studies in animal (rat, murine, canine) and human models of ALI to identify potential ALI candidate genes associated with sepsis and ventilator-associated lung injury. These studies, when combined with innovative in silico bioinformatics approaches, revealed both novel (pre-B-cell colony enhancing factor, myosin light chain kinase) and previously identified (interleukin 6, macrophage migration inhibitory factor) gene candidates. Subsequent single nucleotide polymorphism discovery and genotyping studies revealed polymorphisms that demonstrate an influence on ALI susceptibility in patients. These studies indicate that the candidate gene approach is a robust strategy to provide novel insights into the genetic basis of ALI, and the identification of potentially novel therapeutic targets.Keywords: single nucleotide polymorphism; interleukin 6; pre-B-cell colony enhancing factor Acute lung injury (ALI) is a common and devastating illness in patients with sepsis, pneumonia, or trauma, and carries an annual mortality rate of 30 to 50% (1). Marked by profound inflammation, increased vascular permeability, and alveolar flooding, the acute respiratory failure that is associated with ALI invariably requires mechanically assisted ventilation. Despite advances in care for patients with ALI, the development of sophisticated hemodynamic monitoring technologies, and new insights into the pathogenesis underlying sepsis and ALI, there remains a significant gap in the full translation of this progress into increased ALI survival (2). Furthermore, improved understanding of ALI at both the molecular and population level has not reconciled the heterogeneity in patient susceptibility to ALI or ALI outcomes. Until recently, studies focused on understanding the molecular basis of complex disorders such as ALI were limited to a gene-by-gene approach. However, the capacity for high-throughput sequencing coupled with the mapping of the human genome heralded additional revolutionary technologic breakthroughs with tools for a large-scale analysis of the genome, including rapid, high-throughput gene expression profiling and genotyping (3, 4). Access to the complete genome sequences of prokaryotes, eukaryotic model organisms, as well as the mouse, rat, and dog has sparked efforts to identify specific...

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Cytokine Balance in the Lungs of Patients with Acute Respiratory Distress Syndrome

Cited by 494 publications

References 43 publications

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Functional Genomic Insights into Acute Lung Injury: Role of Ventilators and Mechanical Stress

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