ArticleThe Journal of clinical investigation2013
IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 295 citations in OpenAlex.
- The mechanism of transcutaneous gastric pacing treatment on gastrointestinal motility recovery and inflammation improvement in early-stage acute pancreatitis patients.BMC gastroenterology · 2024Trial
- Pancreatitis cytosorbents (CytoSorb) inflammatory cytokine removal: A Prospective Study (PACIFIC).Medicine · 2019Trial
- Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol.BMJ open · 2017Trial
- Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Refining therapeutic targeting of interleukin-6 by signalling mode selectivity.Nature reviews. Drug discovery · 2026Review
- Expression characteristics and prognostic value of mycoplasma pneumoniae DNA, Interleukin-6, and Interleukin-10 levels in children with mycoplasma pneumoniae pneumonia.Pakistan journal of medical sciences · 2026Article
- Dynamic Assessment of Modified EASIX (m-EASIX) at 48 Hours Predicts Adverse Outcomes in Acute Pancreatitis: A Propensity Score-Matched Study.Medicina (Kaunas, Lithuania) · 2026Article
- Leukocytic ADAM10 and ADAM17 modulate disease severity and systemic outcome in bacterial and viral pneumonia.The European respiratory journal · 2026Article
- Acute pancreatitis: mechanisms and therapeutic approaches.Signal transduction and targeted therapy · 2026Review
- Comparative Evaluation of the Prognostic Accuracy of IL-6 and Angiopoietin-2 for Early Severity Assessment in Acute Pancreatitis: A Systematic Review.Diseases (Basel, Switzerland) · 2026Review
- Neutrophil-macrophage crosstalk network in acute lung injury: feedback circuits linking cytokine storm and cell death.Frontiers in cellular and infection microbiology · 2026Review
- STATs Signaling Pathways in Acute Pancreatitis: Mechanisms and Regulation.International journal of medical sciences · 2026Review
- Role of Interleukin-6 Mediated T Cell Activation in Experimental Acute Pancreatitis.Inflammation · 2025Article
- Prevention, Detection, and Management of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.Gut and liver · 2025Review
- Multi-omics and network pharmacology approaches reveal the mechanism of action of KeKe tablet against post-infectious cough.Chinese medicine · 2025Article
- A novel modulator of IL-6R prevents inflammation-induced preterm birth and improves newborn outcome.EMBO molecular medicine · 2025Article
- TRIM22 governs tumorigenesis and protects against endometrial cancer-associated cachexia by inhibiting inflammatory response and adipose thermogenic activity.Cancer & metabolism · 2025Article
- Potential causal association between gut microbiota, inflammatory cytokines, and acute pancreatitis: A Mendelian randomization study.Journal of intensive medicine · 2025Article
- Effects of lipopolysaccharide administration on thymus damage, antioxidant capacity and immune function in weaned piglets.Journal of veterinary research · 2025Article
- Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis: Novel Mechanisms and Prevention by Drugs.United European gastroenterology journal · 2025Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis-associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.