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Updated: Aug 18, 2026
Lentiviral Vector Preparation for Efficient Gene and MicroRNA Modulation of Peritoneal Cavity Tissue-Resident Macrophages In Vivo in Mice
Published on: February 16, 2024
Macrophage ablation attenuates adenoviral vector-induced pancreatitis
Alexander L Shifrin1, Narendra Chirmule, Yi Zhang
1Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Background:
The objective of these studies is to determine the effects of macrophage ablation on the course of acute viral pancreatitis. Macrophages secrete proinflammatory cytokines triggering local pancreatic and systemic inflammation in the acute phase of virus-induced pancreatitis. We hypothesized that ablation of macrophages should attenuate the host inflammatory response in a mouse model of adenovirus-induced pancreatitis.
Methods:
Liposome-encapsulated dichloromethylene-diphosphonate, a macrophage-depleting agent, was used before direct pancreatic injection of a recombinant adenovirus expressing a marker gene in C57Bl/6 and IL-6 knockout (KO) mice.
Results:
C57Bl/6 mice depleted of macrophages had diminished pancreatic inflammation in the first 24 hours after vector administration. IL-6 KO mice depleted of macrophages had more severe inflammation than similarly treated C57Bl/6 mice. C57Bl/6 mice depleted of macrophages, and IL-6 KO mice had prolonged transgene expression and diminished cytotoxic T lymphocyte responses to adenoviral vector. Mortality was highest in IL-6 KO mice depleted of macrophages. Depletion of macrophages also prevented detectable serum IL-6, IL-10, or IL-12 levels in C57Bl/6 mice.
Conclusions:
The data suggest that macrophages play a role in the acute inflammatory response to viral vector-induced pancreatitis and that IL-6 may be protective. Understanding of the mechanisms that initiate the host immune cascade will allow more effective use of adenoviral vector-based pancreatic gene delivery.
Insights
Macrophage ablation reduced acute inflammation in adenovirus-induced pancreatitis. However, Interleukin-6 (IL-6) knockout mice showed worse inflammation, suggesting IL-6 may be protective in viral pancreatitis.
Area of Science:
- Immunology
- Virology
- Gastroenterology
Background:
- Macrophages contribute to acute inflammation in viral pancreatitis by secreting proinflammatory cytokines.
- Adenovirus-induced pancreatitis serves as a model to study macrophage roles in pancreatic inflammation.
- Hypothesis: Macrophage depletion will reduce the inflammatory response in this model.
Purpose of the Study:
- To investigate the impact of macrophage ablation on acute viral pancreatitis.
- To explore the role of Interleukin-6 (IL-6) in the context of macrophage-mediated inflammation during pancreatitis.
Main Methods:
- Utilized liposome-encapsulated dichloromethylene-diphosphonate for macrophage depletion.
- Administered a recombinant adenovirus vector directly into the pancreas of C57Bl/6 and IL-6 knockout mice.
- Assessed pancreatic inflammation, transgene expression, T lymphocyte responses, and mortality.
Main Results:
- Macrophage-depleted C57Bl/6 mice exhibited reduced pancreatic inflammation within 24 hours.
- IL-6 knockout mice with macrophage depletion showed exacerbated inflammation compared to C57Bl/6 mice.
- Macrophage depletion prolonged transgene expression and reduced cytotoxic T lymphocyte responses.
- Mortality was highest in IL-6 knockout mice depleted of macrophages.
- Serum levels of IL-6, IL-10, and IL-12 were undetectable in macrophage-depleted C57Bl/6 mice.
Conclusions:
- Macrophages are implicated in the acute inflammatory response to adenoviral vector-induced pancreatitis.
- Interleukin-6 (IL-6) appears to have a protective role in this inflammatory process.
- Understanding these immune mechanisms is crucial for optimizing adenoviral vector-based gene delivery to the pancreas.
