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

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.