PMID- 19593412
OWN - NLM
STAT- MEDLINE
DCOM- 20090924
LR  - 20211020
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 15
IP  - 7-8
DP  - 2009 Jul-Aug
TI  - Spermine protects mice against lethal sepsis partly by attenuating surrogate 
      inflammatory markers.
PG  - 275-82
LID - 10.2119/molmed.2009.00062 [doi]
AB  - 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.
FAU - Zhu, Shu
AU  - Zhu S
AD  - Department of Emergency Medicine, North Shore University Hospital, New York 
      University School of Medicine, Manhasset, New York 11030, United States of 
      America.
FAU - Ashok, Mala
AU  - Ashok M
FAU - Li, Jianhua
AU  - Li J
FAU - Li, Wei
AU  - Li W
FAU - Yang, Huan
AU  - Yang H
FAU - Wang, Ping
AU  - Wang P
FAU - Tracey, Kevin J
AU  - Tracey KJ
FAU - Sama, Andrew E
AU  - Sama AE
FAU - Wang, Haichao
AU  - Wang H
LA  - eng
GR  - R01GM070817/GM/NIGMS NIH HHS/United States
GR  - R01 GM062508-05A1/GM/NIGMS NIH HHS/United States
GR  - R01 GM062508/GM/NIGMS NIH HHS/United States
GR  - R01 GM070817/GM/NIGMS NIH HHS/United States
GR  - R01GM063075/GM/NIGMS NIH HHS/United States
GR  - R01 GM062508-01/GM/NIGMS NIH HHS/United States
GR  - R01 GM063075/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090501
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Hbp1 protein, rat)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (lipopolysaccharide, Escherichia coli O111 B4)
RN  - 2FZ7Y3VOQX (Spermine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cells, Cultured
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - HMGB1 Protein/pharmacology
MH  - Inflammation/drug therapy/metabolism/pathology
MH  - Inflammation Mediators/*antagonists & inhibitors/metabolism
MH  - Injections, Intraperitoneal
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages, Peritoneal/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Rats
MH  - Sepsis/*drug therapy/metabolism/pathology
MH  - Spermine/*pharmacology
PMC - PMC2707519
EDAT- 2009/07/14 09:00
MHDA- 2009/09/25 06:00
PMCR- 2009/07/01
CRDT- 2009/07/14 09:00
PHST- 2009/04/28 00:00 [received]
PHST- 2009/04/29 00:00 [accepted]
PHST- 2009/07/14 09:00 [entrez]
PHST- 2009/07/14 09:00 [pubmed]
PHST- 2009/09/25 06:00 [medline]
PHST- 2009/07/01 00:00 [pmc-release]
AID - 09_62_zhu [pii]
AID - 10.2119/molmed.2009.00062 [doi]
PST - ppublish
SO  - Mol Med. 2009 Jul-Aug;15(7-8):275-82. doi: 10.2119/molmed.2009.00062. Epub 2009 
      May 1.