Interleukin-1beta is prominent in the early pulmonary inflammatory response after hepatic injury.
BACKGROUND
Acute lung injury and inflammation can occur after hepatic ischemia/reperfusion or cryoablation. The etiology of this response is uncertain although it involves NF-kappaB-mediated cytokine release from the liver.


METHODS
Inflammation-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 N(2) probe. Hierarchical cluster analysis was performed to identify candidate genes. On the basis of these results, an enzyme-linked immunosorbent assay for interleukin-1beta (IL-1beta) was conducted on serum and pulmonary parenchymal specimens. The time course of IL-1beta transcriptional upregulation in the liver and lungs was evaluated by quantitative reverse transcription/real-time polymerase chain reaction.


RESULTS
Starting 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-1beta was demonstrable in serum within 2 hours postinjury (218 +/- 89 pg/mL vs 0 at baseline, P = .01). In the lung, IL-1beta was more than 4-fold greater at 4 hours than at baseline. Real-time polymerase chain reaction showed a transcription peak of IL-1beta at 30 minutes in the liver, whereas expression in the lungs remained low until 60 minutes, then continued to increase through 4 hours.


CONCLUSIONS
Microarray analysis identified cytokines of the IL-1 family as central components of acute lung injury after hepatic cryoablation. IL-1beta levels increased in both serum and lung tissue over 4 hours after liver injury. Expression of IL-1beta peaked early in the injured liver remnant, followed by subsequent increases in the lungs. Targeted intervention against IL-1beta may ameliorate liver-mediated lung injury.
Glasgow
Sean C
SC
Department of Surgery, Section of Abdominal Transplantation, Washington University, St. Louis, MO 63110, USA.
Ramachandran
Sabarinathan
S
Csontos
Krista A
KA
Jia
Jianluo
J
Mohanakumar
Thalachallour
T
Chapman
William C
WC
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008099:Liver / Q000502:physiology; D008107:Liver Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000150:complications / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology
D007375:Interleukin-1; D012333:RNA, Messenger