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Updated: Aug 17, 2026
A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
Up-regulation of macrophage migration inhibitory factor in infants with acute neonatal necrotizing enterocolitis
1Department orf Surgery, University of Hong Kong, Hong Kong SAR, China. reny@cc.ccf.org
Aims:
To investigate the role of macrophage migration inhibitory factor (MIF) and its downstream cytokine cascade in necrotizing enterocolitis (NEC).
Methods And Results:
The expression of MIF mRNA and protein in NEC guts was assayed by in situ hybridization and immunohistochemistry, respectively. Concentrations of MIF, interleukin (IL)-6 and IL-8 in the serum and in the supernatant of macrophage cultures were examined by ELISA. Increased expression of MIF mRNA and protein was observed in the NEC guts, mainly in the infiltrating macrophages in the mucosa and submucosal layers. Up-regulation of MIF was associated with the accumulation of macrophages and T cells. In addition, serum levels of MIF, IL-6 and IL-8 in NEC patients during the acute stage of the disease were significantly increased. The expression of MIF decreased both locally and systemically after the disease was resolved. MIF was also found to increase the secretion of IL-6 and IL-8 by macrophages isolated from healthy individuals in vitro in NEC.
Conclusions:
MIF acts by stimulating macrophage production of IL-6 and IL-8. This further aggravates the inflammatory process by increasing the infiltration of neutrophils and activating inflammatory cells. The results of this study suggest that MIF plays an important role in the pathogenesis of NEC and may serve as a target for therapeutic intervention in NEC.
Insights
Macrophage migration inhibitory factor (MIF) drives necrotizing enterocolitis (NEC) inflammation by boosting IL-6 and IL-8 production. Lowering MIF may offer a therapeutic strategy for NEC.
Area of Science:
- Immunology
- Gastroenterology
- Neonatal Research
Background:
- Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates.
- The inflammatory pathways involved in NEC pathogenesis require further elucidation.
Purpose of the Study:
- To investigate the role of macrophage migration inhibitory factor (MIF) and its downstream cytokine cascade in NEC.
- To explore MIF as a potential therapeutic target for NEC.
Main Methods:
- Assessed MIF mRNA and protein expression in NEC guts using in situ hybridization and immunohistochemistry.
- Quantified MIF, IL-6, and IL-8 levels in serum and macrophage cultures via ELISA.
- Evaluated MIF's effect on cytokine secretion from macrophages in vitro.
Main Results:
- Increased MIF expression was observed in NEC guts, localized to infiltrating macrophages.
- Elevated serum levels of MIF, IL-6, and IL-8 were found in NEC patients during acute disease.
- MIF stimulation enhanced IL-6 and IL-8 secretion by macrophages.
Conclusions:
- MIF plays a significant role in NEC pathogenesis by exacerbating inflammation.
- MIF promotes IL-6 and IL-8 production, increasing neutrophil infiltration.
- MIF represents a potential therapeutic target for managing NEC.
