The Regulation of Interleukin-8 by Hypoxia in Human Macrophages—A Potential Role in the Pathogenesis of the Acute Respiratory Distress Syndrome (ARDS)

摘要: The acute respiratory distress syndrome (ARDS) represents a form of severe inflammatory lung disease. We have previously demonstrated significantly raised interleukin-8 (IL-8) levels in the lungs at-risk patients that progress to ARDS, and identified alveolar macrophage as an important source this chemokine. wished extend study well-defined group with major trauma, investigate potential mechanisms for rapid intrapulmonary IL-8 generation. Patients trauma underwent brochoalveolar lavage (BAL) were measured BAL fluid by ELISA. Human macrophages derived from peripheral blood monocytes healthy volunteers. Rabbit obtained ex-vivo rabbit lungs. Macrophages culture under normoxic or hypoxic (PO2 26 mmHg) conditions. other proinflammatory mediator expression was ELISA, northern blotting multi-probe RNase protection assay. In higher progressed ARDS compared those did not (n = 56, P 0.0001). High negatively correlated PaO2/FiO2 (r −0.56, < 0.001). human monocyte hypoxia rapidly upregulated protein (within 2 hours) mRNA 30 mins). Acute also increased expression. Hypoxia DNA binding activity AP-1 C/EBP but NF-κB. induced HIF-1 expression, cobaltous ions desferrioxamine mimic induction. downregulated range mediators, including MCP-1 TNF-α. Both pattern cytokine transcription factor activation different seen endotoxin. Rapidly are associated progression trauma. hypoxia, clinically relevant stimulus, selectively upregulates novel activation. may represent one potentially several stimuli responsible intrapulmoanry generation ARDS.