Related Experiment Video
Updated: Dec 28, 2025
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Deletion of macrophage migration inhibitory factor ameliorates inflammation in mice model severe acute pancreatitis
Changju Zhu1, Yanna Liu1, Yaodong Song1
1Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China.
Background:
Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine implicated in sepsis, rheumatoid arthritis and other diseases. However, the role of MIF in acute pancreatitis (AP) remains unclear. This study aims to explore the role of MIF in the pathogenesis of AP using MIF-/- mice (referred to as KO) and the biological effects of pharmacological inhibition of MIF in l-arginine induced AP.
Methods:
AP was induced in C57BL/6 wild-type (referred to as WT) and KO mice by administration of l-arginine. The severity of AP was assessed by serum analysis of amylase and lipase, and of these pro-inflammatory cytokines TNF-α and IL-1β. Histological hematoxylin and eosin (H&E) and immunohistochemical staining of pancreatic tissues were examined for inflammation and expression of pro-inflammatory mediators. We also investigated the biological effects of pharmacological inhibition of MIF activity using ISO-1((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester).
Results:
At 72 h after the induction of AP with l-arginine, significantly lower levels of serum amylase, lipase, TNF-α, and IL-1β were observed in KO mice when compared with WT controls. Histological examination further showed protective effects against pancreatic tissue damage and inflammation, with pancreatic expression of TNF-α, IL-1β and NF-κB p65 markedly reduced. Pharmacological inhibition of MIF activity with ISO-1 markedly mirrored the protective effect seen in the KO AP model providing further evidence that MIF is involved in the pathogenesis of AP.
Conclusion:
Our data provided strong evidence for the participation of MIF in the pathogenesis of AP and subsequent inflammatory response. The genetic ablation of MIF or its inhibition with pharmacological agents significantly ameliorated the severity of AP.
Insights
Macrophage migration inhibitory factor (MIF) deficiency or inhibition significantly reduces acute pancreatitis (AP) severity. Genetic knockout or pharmacological blocking of MIF protects against l-arginine-induced AP, lowering inflammatory markers and tissue damage.
Area of Science:
- Immunology
- Gastroenterology
- Pathophysiology
Background:
- Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine involved in various diseases.
- The specific role of MIF in the pathogenesis of acute pancreatitis (AP) has not been clearly defined.
- This study investigates MIF's contribution to AP using genetic and pharmacological approaches.
Purpose of the Study:
- To elucidate the role of MIF in the development of acute pancreatitis.
- To evaluate the therapeutic potential of inhibiting MIF in AP models.
Main Methods:
- Acute pancreatitis (AP) was induced in wild-type (WT) and MIF knockout (KO) mice using l-arginine.
- Serum levels of amylase, lipase, TNF-α, and IL-1β were measured to assess AP severity.
- Histological analysis and immunohistochemistry were performed on pancreatic tissues; pharmacological inhibition was studied using ISO-1.
Main Results:
- MIF knockout mice exhibited significantly reduced serum amylase, lipase, TNF-α, and IL-1β levels compared to WT controls.
- Histological examination revealed reduced pancreatic tissue damage and inflammation in KO mice.
- Pharmacological inhibition of MIF with ISO-1 mimicked the protective effects observed in KO mice, confirming MIF's role.
Conclusions:
- Macrophage migration inhibitory factor (MIF) plays a significant role in the pathogenesis of acute pancreatitis.
- Genetic deletion or pharmacological inhibition of MIF effectively ameliorates AP severity and associated inflammation.
- Targeting MIF presents a potential therapeutic strategy for managing acute pancreatitis.
Related Concept Videos
01:24Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
01:27Acute Pancreatitis I: Introduction
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include: