# DNA Vaccination Against Macrophage Migration Inhibitory Factor Protecting Mice From Experimental Pancreatitis

**Authors:** Tatsuya Ohkawara, Naoto Okubo, Shunsuke Ohnishi

PMC · DOI: 10.7759/cureus.102441 · Cureus · 2026-01-27

## TL;DR

A DNA vaccine targeting MIF reduces inflammation and protects mice from experimental pancreatitis.

## Contribution

A novel DNA vaccine strategy using auto-MIF antibodies to treat pancreatitis is demonstrated in mice.

## Key findings

- MIF-DNA vaccination increased MIF antibody titers and reduced MIF levels in mice with pancreatitis.
- The vaccine suppressed inflammatory markers like IL-1β and MCP-1 in the pancreas and serum.
- Pancreatic HSP70 levels were upregulated in vaccinated mice, indicating cytoprotective effects.

## Abstract

Objective

Macrophage migration inhibitory factor (MIF) has a pivotal role in the development of gastroenterological diseases, including pancreatitis. In this study, we aimed to explore the effect of deoxyribonucleic acid (DNA) vaccination producing an auto-MIF antibody on experimental pancreatitis and to provide additional evidence that MIF affects the development of pancreatitis.

Methods

Mice were treated with an MIF-DNA vaccine by introducing oligonucleotides encoding a helper T epitope into the cDNA sequence of murine MIF by in vivo electroporation. Thereafter, experimental pancreatitis was induced by seven repeated intraperitoneal injections of cerulein (50 μg/kg). Histological findings were evaluated in the pancreas. The levels of MIF, monocyte chemoattractant protein-1 (MCP-1), IL-1β, and heat shock protein 70 (HSP70) were analyzed with enzyme-linked immunosorbent assay (ELISA).

Results

The titer of MIF antibody was increased in the serum of mice 8 weeks after the treatment with MIF-DNA vaccine. In cerulein-induced pancreatitis, the histological findings in the pancreas were ameliorated in MIF-DNA vaccinated mice. The serum levels of MIF were lower in MIF-DNA vaccinated mice than those in mock-treated mice with pancreatitis. The increases in the serum and pancreatic levels of IL-1β and the serum level of MCP-1 were suppressed in MIF-DNA-vaccinated mice given cerulein. Furthermore, the pancreatic HSP70 level was upregulated in MIF-DNA-vaccinated mice given cerulein.

Conclusion

MIF-DNA vaccination protected mice from cerulein-induced pancreatitis via anti-inflammatory and cytoprotective effects. MIF-DNA vaccination may be an additional option for the treatment of pancreatitis.

## Linked entities

- **Proteins:** MIF (macrophage migration inhibitory factor), CCL2 (C-C motif chemokine ligand 2), IL1B (interleukin 1 beta), HSPA1A (heat shock protein family A (Hsp70) member 1A)
- **Chemicals:** cerulein (PubChem CID 16129675)
- **Diseases:** pancreatitis (MONDO:0004982)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Lipg (lipase G, endothelial type) [NCBI Gene 16891] {aka 3110013K01Rik, EL, lipase, mEDL}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mif (macrophage migration inhibitory factor (glycosylation-inhibiting factor)) [NCBI Gene 17319] {aka DER6, GIF, Glif}, Hspa1b (heat shock protein family A (Hsp70) member 1B) [NCBI Gene 15511] {aka HSP70B1, Hsp70, Hsp70-1, Hsp70.1, hsp68}, Blnk (B cell linker) [NCBI Gene 17060] {aka BASH, Bca, Ly-57, Ly57, Lyw-57, SLP-65}, Th (tyrosine hydroxylase) [NCBI Gene 21823], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}
- **Diseases:** colitis (MESH:D003092), benign gastrointestinal diseases (MESH:D005767), infections (MESH:D007239), arthritis (MESH:D001168), death (MESH:D003643), necrosis (MESH:D009336), pancreatic damage (MESH:D010182), gastritis (MESH:D005756), tissue injury (MESH:D017695), inflammatory bowel disease (MESH:D015212), Proinflammatory cytokines (MESH:D000080424), hepatitis (MESH:D056486), failures (MESH:D051437), Lung Injury (MESH:D055370), Pancreatitis (MESH:D010195), edema (MESH:D004487), inflammation (MESH:D007249), gastroenterological diseases (MESH:D004194), hemorrhage (MESH:D006470), dermatitis (MESH:D003872)
- **Chemicals:** H&amp;E. (MESH:D006371), PBS (-), Cerulein (MESH:D002108), formalin (MESH:D005557), diethyl ether (MESH:D004986), nitrogen (MESH:D009584), paraffin (MESH:D010232), thiopental (MESH:D013874), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12947605/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947605/full.md

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Source: https://tomesphere.com/paper/PMC12947605