In:
Pulmonary Circulation, Wiley, Vol. 4, No. 2 ( 2014-06), p. 280-288
Abstract:
Patients with acute respiratory distress syndrome (ARDS) exhibit elevated levels of interleukin‐6 (IL‐6), which correlate with increased morbidity and mortality. The exact role of IL‐6 in ARDS has proven difficult to study because it exhibits either pro‐ or anti‐inflammatory actions in mouse models of lung injury, depending on the model utilized. In order to improve understanding of the role of this complex cytokine in ARDS, we evaluated IL‐6 using the clinically relevant combination of lipopolysaccharide (LPS) and ventilator‐induced lung injury (VILI) in IL‐6 −/– mice. Bronchoalveolar lavage fluid (BAL), whole‐lung tissue, and histology were evaluated for inflammatory markers of injury. Transendothelial electrical resistance was used to evaluate the action of IL‐6 on endothelial cells in vitro. In wild‐type mice, the combination model showed a significant increase in lung injury compared to either LPS or VILI alone. IL‐6 −/– mice exhibited a statistically significant decrease in BAL cellular inflammation as well as lower histologic scores for lung injury, changes observed only in the combination model. A paradoxical increase in BAL total protein was observed in IL‐6 −/– mice exposed to LPS, suggesting that IL‐6 provides protection from vascular leakage. However, in vitro data showed that IL‐6, when combined with its soluble receptor, actually caused a significant increase in endothelial cell permeability, suggesting that the protection seen in vivo was likely due to complex interactions of IL‐6 and other inflammatory mediators rather than to direct effects of IL‐6. These studies suggest that a dual‐injury model exhibits utility in evaluating the pleiotropic effects of IL‐6 in ARDS on inflammatory cells and lung endothelium.
Type of Medium:
Online Resource
ISSN:
2045-8940
,
2045-8940
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2638089-4
