title: The β-human chorionic gonadotropin-related peptide LQGV reduces mortality and inflammation in a murine polymicrobial sepsis model.
abstract: OBJECTIVE
  Mortality in sepsis remains high and efforts to modulate the inflammatory response so far mostly failed to improve survival. The human chorionic gonadotropin-related tetrapeptide LQGV was recently shown to exert anti-inflammatory activity. The aim of this study was to assess the effect of LQGV on cecal ligation and puncture-induced mortality and inflammation.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male C57BL/6 mice.
  
  
  METHODS
  To examine the effect of LQGV by itself on cecal ligation and puncture-induced mortality and inflammation, C57BL/6 mice were exposed to a moderate cecal ligation and puncture procedure (40% ligation and double puncture) with a mortality rate of approximately 80% within 5 days in control mice. In addition, to examine whether LQGV was of additive value to standard sepsis care (antibiotics and fluid resuscitation), a more severe cecal ligation and puncture procedure was used (80% ligation and double puncture), yielding approximately 100% mortality within 12 days in control mice. LQGV (5 mg/kg body weight), phosphate-buffered saline (as control), or dexamethasone (2.5 mg/kg body weight) was administered perioperatively. Survival was monitored for 21 days and inflammatory markers were determined in plasma, peritoneal cavity, and lungs.
  
  
  RESULTS
  LQGV significantly improved survival from 20% to 50% during the first 5 days after moderate cecal ligation and puncture. This was associated with reduced cytokine and E-selectin levels in peritoneal lavage fluid, lungs, and, to a lesser extent, in plasma. LQGV treatment also reduced pulmonary nuclear factor-κB activation and pulmonary damage. In the severe cecal ligation and puncture model, LQGV combined with fluid resuscitation and antibiotics resulted in significantly better survival (70%) than that observed with fluid resuscitation and antibiotics alone (30%).
  
  
  CONCLUSIONS
  LQGV improves survival after cecal ligation and puncture. This is likely established by a modest reduction of the acute inflammatory response through a nuclear factor-κB-dependent mechanism. Furthermore, LQGV may be a valuable additive next to the standard care in polymicrobial sepsis.
authors.affiliation: Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: van den Berg
authors.forename: Willem A
authors.initials: WA
authors.lastname: Dik
authors.forename: Marten
authors.initials: M
authors.lastname: van der Zee
authors.forename: Fred
authors.initials: F
authors.lastname: Bonthuis
authors.forename: Conny
authors.initials: C
authors.lastname: van Holten-Neelen
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Dingjan
authors.forename: Robbert
authors.initials: R
authors.lastname: Benner
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Nisar A
authors.initials: NA
authors.lastname: Khan
authors.forename: Ron W F
authors.initials: RW
authors.lastname: de Bruin
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D008026:Ligation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010533:Peritoneal Lavage; D012329:RNA, Bacterial / Q000032:analysis; D011897:Random Allocation; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000401:mortality
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D016207:Cytokines; D012329:RNA, Bacterial; D003907:Dexamethasone