title: Heparin inhibits burn-induced spleen cell apoptosis by suppressing interleukin-1 expression.
abstract: BACKGROUND
  Epidermal burn injury may trigger significant apoptosis of the spleen cells, which might be caused by a burn-induced systemic inflammatory reaction. Heparin has been shown to possess anti-inflammatory properties. Interleukin 1 (IL-1) is centrally important among pro-inflammatory cytokines. We hypothesized that heparin might inhibit burn-induced apoptosis in the spleen via suppression of the IL-1 pathway.
  
  
  METHODS
  Burn injury was performed on IL-1 R+/+ ( IL-1 receptor wild-type mouse) and IL-1 R-/- (IL-1 receptor knock-out mouse) mice, and they were then treated with heparin, saline or IL-1 receptor antagonist IL-Ra. Apoptosis, IL-1α and IL-1β expression were assessed in the spleens and serum. Survival curve analysis was further applied to elucidate the mechanism of heparin's protective properties.
  
  
  RESULTS
  Burn induced significant apoptosis (sham: 3.6%± 2.1% vs. burn: 28.8%± 5.9%; P < 0.001) and remarkable expression o IL-1α and IL-1β in the mouse spleens and serum. Heparin reduced the burn-induced apoptosis in the spleens (heparin treated: 8.6%± 3.4%, P < 0.005), which could be blocked by IL-1Ra. Heparin markedly decreased both IL-1α and IL-1β expression in the spleens and serum of burned mice. IL-1 R-/- mice demonstrated considerably less apoptosis in the spleens and had a higher survival rate after burns. Heparin did not significantly decrease apoptosis in the spleen and the mortality rate in IL-1 R-/- mice after burns.
  
  
  CONCLUSIONS
  Heparin inhibits burn-induced apoptosis of the spleen cells by suppressing IL-1 expression in mice.
authors.affiliation: Department of Pharmacology, the Provincial Key Lab of Clinical Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Songfeng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, the Provincial Key Lab of Clinical Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, the Provincial Key Lab of Clinical Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, the Provincial Key Lab of Clinical Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, the Provincial Key Lab of Clinical Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Zujiang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, the Provincial Key Lab of Clinical Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China. Email: johyu@zzu.edu.cn.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism*; D006493:Heparin / Q000627:therapeutic use*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D006493:Heparin