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- Title
Spermine Protects Mice Against Lethal Sepsis Partly by Attenuating Surrogate Inflammatory Markers.
- Authors
Shu Zhu; Ashok, Mala; Jianhua Li; Wei Li; Huan Yang; Ping Wang; Tracey, Kevin J.; Sama, Andrew E.; Haichao Wang
- 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-α receptor I [sTNFRI], and soluble tumor necrosis factor-α 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.
- Subjects
SPERMINE; RETICULO-endothelial system; TUMOR necrosis factors; DRUG receptors; INTERLEUKIN-6; LABORATORY mice; MEDICAL research
- Publication
Molecular Medicine, 2009, Vol 15, Issue 7/8, p275
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2009.00062