Alterations of leptin in the course of inflammation and severe sepsis

Abstract

Abstract Background The adipokine leptin regulates energy expenditure, vascular function, bone and cartilage growth as well as the immune system and systemic inflammatory response. Several activating effects towards T cells, monocytes, endothelium cells and cytokine production have been reported suggesting a protective role of leptin in the setting of an acute systemic inflammation. However, the pathophysiological role of leptin during severe sepsis is currently not elucidated in detail. This study aims to investigate leptin expression in cultured human adipocytes within an inflammatory model and in patients suffering from severe sepsis and evaluates treatment effects of drotrecogin alpha (activated) (DAA), the recombinant form of human activated protein C. Methods In an in-vitro inflammatory model of adipocyte cell-culture the effect of DAA on leptin mRNA expression was evaluated. Synthesis of mRNA was measured by quantitative polymerase chain reaction (qPCR). Additionally, supernatants of these adipocytes as well as serum levels of adiponectin were measured in blood of 104 severe septic patients by ELISA-method. 26 patients were treated with DAA (DAA+), 78 patients were not treated with DAA (DAA-). Results Stimulation of human adipocytes with TNF alpha over 6 and 24 hours resulted in a significant decrease by 46% and 59% of leptin mRNA transcripts compared to un-stimulated controls (p Conclusions Leptin appears to be involved in the pathogenesis of a systemic inflammatory response during sepsis. Administration of DAA significantly increased leptin expression. The specific mechanism or even benefit of DAA towards leptin needs further ongoing research.

Keywords

• Adipocytes
• Drotrecogin alpha (activated)
• Leptin
• mRNA
• Sepsis
• Supernatants