Abstract:
:Granulocyte-macrophage colony-stimulating factor (GM-CSF) is used to ameliorate neutropenia in patients after antineoplastic treatment. It has also been suggested as an adjunct treatment in septic patients; however, the recruitment and priming of leukocytes by GM-CSF bears the hazard of a hyperinflammatory response. In particular, the role of GM-CSF in pulmonary functions in septic lungs is still unclear. Therefore, we pretreated rats in vivo with GM-CSF (50 microg/kg, intravenous) and assessed the pulmonary functions of their subsequently prepared isolated perfused lungs when exposed to subtoxic concentrations of lipopolysaccharide (LPS, 2 microg/ml). These lungs showed enhanced expression of cyclooxygenase 2 (COX-2), a significant increase in thromboxane (TX) and tumor necrosis factor (TNF) release into the venous perfusate, and bronchoconstriction. COX-2 inhibition or blocking of the TX receptor abolished the GM-CSF/LPS-induced bronchoconstriction, but not the TNF release. Neutralizing antibodies against TNF did not prevent GM-CSF/LPS-induced bronchoconstriction. After GM-CSF pretreatment, massive neutrophil invasion into the lung occurred. Neutropenic rats were protected against GM-CSF/ LPS-induced lung injury. Similar results were obtained in rats pretreated with G-CSF instead of GM-CSF. We conclude that GM-CSF pretreatment exacerbates pulmonary injury by low-dose LPS via COX-2 expression, TX release, and bronchoconstriction by initiating neutrophil invasion and activation.
journal_name
Am J Respir Crit Care Medauthors
Wollin L,Uhlig S,Nüsing R,Wendel Adoi
10.1164/ajrccm.163.2.2004031keywords:
subject
Has Abstractpub_date
2001-02-01 00:00:00pages
443-50issue
2eissn
1073-449Xissn
1535-4970journal_volume
163pub_type
杂志文章abstract::In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing ai...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2003-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2012-08-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2008-06-01 00:00:00