Decreased neutrophil counts prolong inflammation in acute pancreatitis and cause inflammation spillover to distant organs

Pancreatology. 2023 Dec;23(8):911-918. doi: 10.1016/j.pan.2023.10.020. Epub 2023 Nov 3.

Abstract

Background/objective: Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics.

Methods: We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G-CSF-KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 μg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically.

Results: The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G-CSF-KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G-CSF-KO mice, indicating prolonged inflammation.

Conclusion: Prolonged inflammation was observed in the G-CSF-KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase.

Keywords: Animal study; Inflammatory response; Neutrophils; Pancreas.

MeSH terms

  • Acute Disease
  • Animals
  • Ceruletide / toxicity
  • Disease Models, Animal
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Neutrophils
  • Pancreas / pathology
  • Pancreatitis* / chemically induced
  • Pancreatitis* / pathology

Substances

  • Ceruletide
  • Granulocyte Colony-Stimulating Factor