OBJECTIVES: Alarmin high mobility group box 1 (HMGB1) is essential for correct DNA folding and transcription. It can be released from damaged cells or secreted by stimulated cells. HMGB1 has been detected in serum or plasma as a late marker of sepsis, but its suitability as a marker of sepsis has been disputed. METHODS: One-week-old germ-free piglets were orally infected/colonized with enteric bacterial pathogens (Salmonella Typhimurium or Escherichia coli O55) or with probiotic bacteria (E. coli Nissle 1917) for 24 h. The transcriptions of HMGB1, interleukin (IL)-8, tumor necrosis factor (TNF)-α, and IL-10 (quantitative reverse transcription and polymerase chain reaction), their protein levels (ELISA), and clinical state of the piglets (somnolence, anorexia, diarrhea, tachycardia, tachypnea, and tremor) were estimated. RESULTS: The piglets infected with enteric pathogens suffered from infections. HMGB1 was transcribed in the terminal ileum constitutively, regardless of any bacterial presence. In contrast, the transcription of cytokines was upregulated by virulent bacteria. HMGB1, IL-8, and TNF-α levels in the ileum were increased by both enteric pathogens, while IL-10 levels increased in E. coli O55-infected piglets only. HMGB1 significantly increased in the plasma of piglets infected with virulent E. coli only, but cytokine levels were in most cases increased by both virulent bacteria. HMGB1 and cytokine levels in ileum lavages and plasma of piglets colonized with probiotic E. coli remained comparable to those of the non-stimulated germ-free piglets. CONCLUSION: The local and systemic expression of HMGB1, its relationship to the inflammatory cytokines, and clinical findings showed HMGB1 as a suitable marker of severity of sepsis in the gnotobiotic piglet infection model.
- MeSH
- Bacterial Infections blood immunology microbiology MeSH
- Biomarkers blood MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Escherichia coli growth & development MeSH
- Germ-Free Life MeSH
- Ileum metabolism microbiology MeSH
- Interleukin-10 blood MeSH
- Interleukin-8 blood MeSH
- Disease Models, Animal MeSH
- Animals, Newborn blood immunology microbiology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Swine MeSH
- HMGB1 Protein blood MeSH
- Diarrhea MeSH
- Salmonella typhimurium growth & development MeSH
- Sepsis blood immunology microbiology MeSH
- Severity of Illness Index MeSH
- Tachycardia MeSH
- Tumor Necrosis Factor-alpha blood MeSH
- Tremor MeSH
- Inflammation blood immunology microbiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Bifidobacterium metabolism MeSH
- Enterocytes enzymology microbiology MeSH
- Research Support as Topic MeSH
- Germ-Free Life MeSH
- Hydrolases biosynthesis MeSH
- Mice MeSH
- Animals, Newborn microbiology MeSH
- Probiotics MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH
