Spermine protects mice against lethal sepsis partly by attenuating surrogate inflammatory markers
Open accessAbstract
The pathogenesis of sepsis is partly attributable to dysregulated inflammatory response mediated by pathogen-associated molecular patterns (PAMPs) (for example, endotoxin) and damage-associated molecular patterns (DAMPs) (for example, high-mobility group box 1 [HMGB1]). An endogenous ubiquitous polyamine, spermine, inhibits endotoxin-induced cytokine release in vitro, but its capacities to attenuate sepsis- and HMGB1-induced inflammatory responses was previously unknown. We thus tested the hypothesis that spermine protects mice against lethal sepsis by attenuating sepsis-induced local and systemic inflammatory responses. Intraperitoneal (i.p.) administration of spermine (10 mg/kg, twice daily, for 3 d) conferred a significant protection against lethal sepsis. The protective effects were associated with a significant reduction in peritoneal and serum levels of several surrogate markers of sepsis (for example, Interleukin-6 [IL-6], keratinocyte-derived chemokine [KC], monocytes chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-2 [MIP-2], tissue inhibitor of metalloproteinase-1 [TIMP-1], soluble tumor necrosis factor-alpha receptor I [sTNFRI], and soluble tumor necrosis factor-alpha receptor II [sTNFRII]) during a late stage of sepsis. In vitro, spermine effectively inhibited HMGB1-induced release of the above surrogate markers in peritoneal macrophages. Thus, spermine confers protection against lethal sepsis partly by attenuating sepsis- and HMGB1-induced inflammatory responses.
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Spermine administration has protective anti-inflammatory effects in mouse models of localized and systemic inflammation.
“spermine administration exhibits protective anti-inflammatory effects in mouse models of both localized and systemic inflammation (Steege et al., 1999; M. Zhang et al., 1997; S. Zhu et al., 2009).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as S. Zhu et al., 2009
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- Authors
- Zhu, S., Ashok, M., Li, J., Li, W., Yang, H., Wang, P., Tracey, K. J., Sama, A. E., & Wang, H.
- Affiliations
- Feinstein Institute for Medical Research (US)
- North Shore University Hospital (US)
- Corresponding author
- Wang, Haichao
- Venue
- Molecular Medicine
- Published
- 2009-05-01
- Volume
- 15
- Issue
- 7-8
- Pages
- 275-282
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC2707519
- OpenAlex
- W8739995
- Cited by
- 109
- References
- 45
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 11
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Feinstein Institutes for Medical Research
- National Institute of General Medical Sciences (R01GM063075, R01GM070817, R01GM062508)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- spermine, sepsis, HMGB1, polyamines, inflammation, endotoxin, cytokines, chemokines, peritoneal macrophages, soluble TNF receptors, TIMP-1, MCP-1, CXCL2, KC, interleukin-6, damage-associated molecular patterns, pathogen-associated molecular patterns
- MeSH terms
- Analysis of Variance, Animals, Cells, Cultured, Disease Models, Animal, Inflammation, Injections, Intraperitoneal, Lipopolysaccharides, Male, Mice, Inbred BALB C, Spermine, Biomarkers, Cytokines, Macrophages, Peritoneal, Sepsis, Inflammation Mediators, HMGB1 Protein, Mice, Rats
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