The somatostatin receptor 2A as a possible therapeutic target in sepsis and associated liver-dysfunction

Acronym: SomatostatinR

Principal Investigator: Dipl. Biol. Isabell Lenhardt 

Scientific Advisor: apl. Prof. Dr. med. habil. Amelie Lupp

Research Area: D Sepsis related Organ Failure

Project Number: D1.6

Duration: 01.03.2011 - 28.02.2014

Module: PhD Fellowship

The Problem

About 20 to 25% of patients with sepsis and associated organ failure quite early display an impaired liver function, which in severe cases can result in acute liver failure. However, despite extensive research efforts no specific therapy exists so far for the treatment of liver failure in sepsis. Since literature data suggest an immunomodulatory action of somatostatin, the aim of our investigations is to elucidate whether somatostatin receptors (especially the somatostatin receptor 2A [SSTR2 A]) can serve as possible targets for the treatment of liver dysfunction in sepsis e.g. using long-acting somatostatin analogues.

Results so far

Using two different models for the induction of a systemic inflammatory reaction in mice, intraperitoneal administration of lipopolysaccharides (LPS) and peritoneal contamination and infection with human stool bacteria (PCI), it could be shown that SSTR2A knockout mice are more susceptible to the induction of a systemic inᴀammation than wild-type and heterozygous animals. These differences between the SSTR2A mouse genotypes were seen not only with respect to liver function and to the oxidative state in liver tissue but also with regard to other organ systems (lung, cardiovascular system, kidney), thus pointing to an involvement of the SSTR2A in systemic inᴀammatory reactions.

Further experiments carried out subsequently revealed (as expected), that a concomitant treatment of wild-type mice with the long-acting somatostatin analogue octreotide was able to reduce the LPS induced effects both in liver and in different other organ systems. In contrast (and as also expected), no protective effects were observed in SSTR2A knockout mice.

Contact 

apl. Prof. Dr. med. habil. Amelie Lupp

Tel. +49 (0)3641 - 9 32 56 78

Universitätsklinikum Jena
Institut für Pharmakologie und Toxikologie
Drackendorfer Str. 1
07747 Jena