title: Dual role of leukotriene B4 receptor type 1 in experimental sepsis.
abstract: BACKGROUND
  The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis.
  
  
  METHODS
  Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate.
  
  
  RESULTS
  The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice.
  
  
  CONCLUSIONS
  U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiu-juan
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Fu
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology and Intensive Care, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jin-bao
authors.initials: JB
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: jfwang@smmu.edu.cn.
authors.forename: Jia-feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: deng_x@yahoo.com.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Deng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005233:Fatty Alcohols / Q000633:toxicity*; D006018:Glycols / Q000633:toxicity*; D007975:Leukotriene B4 / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D018102:Receptors, Leukotriene B4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*
chemical_list: D005233:Fatty Alcohols; D006018:Glycols; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; C062137:U 75302; D007975:Leukotriene B4
keywords: BLT1; Leukotriene B4; Sepsis; Survival