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Updated: Jun 21, 2026
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Spermine protects mice against lethal sepsis partly by attenuating surrogate inflammatory markers
Shu Zhu1, Mala Ashok, Jianhua Li
1Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, United States of America.
Abstract:
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.
Insights
Spermine, an endogenous polyamine, protects mice from lethal sepsis by reducing inflammatory responses. This study shows spermine attenuates sepsis- and high-mobility group box 1 (HMGB1)-induced inflammation, offering a potential therapeutic avenue.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Sepsis pathogenesis involves dysregulated inflammatory responses to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
- Spermine, a ubiquitous polyamine, is known to inhibit endotoxin-induced cytokine release in vitro.
- The effects of spermine on sepsis- and HMGB1-induced inflammation were previously uncharacterized.
Purpose of the Study:
- To investigate the protective effects of spermine against lethal sepsis in mice.
- To determine if spermine attenuates sepsis-induced local and systemic inflammatory responses.
- To assess spermine's in vitro efficacy in inhibiting HMGB1-induced inflammatory mediator release.
Main Methods:
- Mice were administered spermine intraperitoneally (10 mg/kg, twice daily for 3 days) and then subjected to a lethal sepsis model.
- Peritoneal and serum levels of sepsis surrogate markers (e.g., IL-6, KC, MCP-1, MIP-2, TIMP-1, sTNFR I, sTNFR II) were measured.
- In vitro experiments assessed spermine's effect on HMGB1-induced inflammatory marker release from peritoneal macrophages.
Main Results:
- Spermine administration conferred significant protection against lethal sepsis.
- Spermine treatment markedly reduced peritoneal and serum levels of multiple sepsis surrogate markers during the late stage of sepsis.
- In vitro, spermine effectively inhibited HMGB1-induced release of these inflammatory markers in peritoneal macrophages.
Conclusions:
- Spermine confers protection against lethal sepsis in a mouse model.
- The protective mechanism involves the attenuation of both sepsis- and HMGB1-induced inflammatory responses.
- Spermine demonstrates potential as a therapeutic agent for sepsis by modulating key inflammatory pathways.
