The β-human chorionic gonadotropin-related peptide LQGV reduces mortality and inflammation in a murine polymicrobial sepsis model.
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.
van den Berg
Jan Willem
JW
Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.
Dik
Willem A
WA
van der Zee
Marten
M
Bonthuis
Fred
F
van Holten-Neelen
Conny
C
Dingjan
Gemma M
GM
Benner
Robbert
R
Ijzermans
Jan N M
JN
Khan
Nisar A
NA
de Bruin
Ron W F
RW
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
D018997:Chorionic Gonadotropin, beta Subunit, Human; D016207:Cytokines; D012329:RNA, Bacterial; D003907:Dexamethasone