Interleukin-1β is prominent in the early pulmonary inflammatory response after hepatic injury


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Abstract

BackgroundAcute lung injury and inflammation can occur after hepatic ischemia/reperfusion or cryoablation. The etiology of this response is uncertain although it involves NF-κB–mediated cytokine release from the liver.MethodsInflammation-specific complementary DNA microarrays were utilized to evaluate cytokine upregulation in mouse lung at 4 hours after partial-volume hepatic cryoablation with a recirculating liquid N2 probe. Hierarchical cluster analysis was performed to identify candidate genes. On the basis of these results, an enzyme-linked immunosorbent assay for interleukin-1β (IL-1β) was conducted on serum and pulmonary parenchymal specimens. The time course of IL-1β transcriptional upregulation in the liver and lungs was evaluated by quantitative reverse transcription/real-time polymerase chain reaction.ResultsStarting with a pool of 35 genes generated from normalization and variation filtration, unsupervised hierarchical clustering clearly distinguished lungs of hepatic cryo–injured mice from controls. Genes from the IL-1-family were prominent in the signature. IL-1β was demonstrable in serum within 2 hours postinjury (218 ± 89 pg/mL vs 0 at baseline, P = .01). In the lung, IL-1β was more than 4-fold greater at 4 hours than at baseline. Real-time polymerase chain reaction showed a transcription peak of IL-1β at 30 minutes in the liver, whereas expression in the lungs remained low until 60 minutes, then continued to increase through 4 hours.ConclusionsMicroarray analysis identified cytokines of the IL-1 family as central components of acute lung injury after hepatic cryoablation. IL-1β levels increased in both serum and lung tissue over 4 hours after liver injury. Expression of IL-1β peaked early in the injured liver remnant, followed by subsequent increases in the lungs. Targeted intervention against IL-1β may ameliorate liver-mediated lung injury.

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