Synthetic oligopeptides related to the β-subunit of human chorionic gonadotropin attenuate inflammation and liver damage after (Trauma) hemorrhagic shock and resuscitation

Received 31 Mar 2008; first review completed 11 Apr 2008; accepted in final form 6 May 2008ABSTRACT—Severe hemorrhagic shock (HS) followed by resuscitation induces a massive inflammatory response, whichmay culminate into systemic inflammatory response syndrome, multiple organ dysfunction syndrome, and, finally, death.Treatments that effectively prevent this inflammation are limited so far. In a previous study, we demonstrated thatsynthetic oligopeptides related to the primary structure of human chorionic gonadotropin (HCG) can inhibit theinflammatory response and mortality that follow high-dose LPS-induced inflammation. Considering this powerful anti-inflammatory effect, we investigated whether administration of similar synthetic HCG-related oligopeptides (LQGV, AQGV,LAGV) during HS were able to attenuate the inflammatory response associated with this condition. Hemorrhagic shockwas induced in rats for 60 min by blood withdrawal until a MAP of 40 mmHg was reached. Rats received a single injectionwith one of the hCG-related oligopeptides (LQGV, AQGV or LAGV) or 0.9% NaCl solution as control 30 min afterinduction of HS. Treatment with LQGV, AQGV, or LAGV prevented systemic release of TNF-! and IL-6 and wasassociated with reduced TNF-!, IL-6, and E-selectin mRNA transcript levels in the liver. LQGV treatment preventedneutrophil infiltration into the liver and was associated with reduced liver damage. Our data suggest that HCG-relatedoligopeptides, in particular LQGV, have therapeutic potential by attenuating the life-threatening inflammation and organdamage that is associated with (trauma) HS and resuscitation.KEYWORDS—Hemorrhagic shock, HCG-related oligopeptides, cytokines, adhesion molecules, organ damage