ArticleProceedings of the National Academy of Sciences of the United States of America2008
Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 77 citations in OpenAlex.
- Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation.The Journal of clinical investigation · 2020Trial
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Prospective observational study and mechanistic evidence showing lipolysis of circulating triglycerides worsens hypertriglyceridemic acute pancreatitis.The Journal of clinical investigation · 2024Observational
- Interleukins: pathophysiological role in acute pancreatitis.Archives of medical science : AMS · 2024Article
- Severe acute pancreatitis exhibits distinct cytokine signatures and trajectories in humans: a prospective observational study.American journal of physiology. Gastrointestinal and liver physiology · 2022Observational
- Circulating monocytes in acute pancreatitis.Frontiers in immunology · 2022Review
- Acute pancreatic injuries: A complication of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with cytotoxic immunocell activation.Journal of the American Academy of Dermatology · 2021Article
- NLRP3 Inflammasome-Mediated Inflammation in Acute Pancreatitis.International journal of molecular sciences · 2020Review
- Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer.Pancreas · 2019Review
- Organ Failure Due to Systemic Injury in Acute Pancreatitis.Gastroenterology · 2019Review
- Role of obesity in the release of extracellular nucleosomes in acute pancreatitis: a clinical and experimental study.International journal of obesity (2005) · 2019Article
- Activin in acute pancreatitis: Potential risk-stratifying marker and novel therapeutic target.Scientific reports · 2017Article
- Effects of Lactobacillus plantarum Strain OLL2712 Culture Conditions on the Anti-inflammatory Activities for Murine Immune Cells and Obese and Type 2 Diabetic Mice.Applied and environmental microbiology · 2017Article
- Pathogenic mechanisms of pancreatitis.World journal of gastrointestinal pharmacology and therapeutics · 2017Review
- Article
- Inflammasomes in pancreatic physiology and disease.American journal of physiology. Gastrointestinal and liver physiology · 2015Review
- Inhibition of the nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 inflammasome reduces the severity of experimentally induced acute pancreatitis in obese mice.Translational research : the journal of laboratory and clinical medicine · 2014Article
- Site-specific changes in cytokine response to septic dose of lipopolysaccharide in ovariectomized female rats.Journal of endocrinological investigation · 2014Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.
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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.