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BMC Infectious Diseases

, 12:217

Bacterial and fungal diseases

Abstract

BackgroundThe 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.

MethodsIn 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-.

ResultsStimulation 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 < 0.05. Leptin levels of supernatants of adipocyte culture decreased by 25% and 23% p < 0.05 after incubation with TNF alpha after 6 and 24 hours. Incubation with DAA at 50 ng-ml DAA and 5 μg-ml doubled mRNA expression significantly at 24 hours p < 0.05 but not at 6 hours. From day 1 to day 3 of sepsis, leptin levels increased in DAA+ compared to DAA- patients p<0.10.

ConclusionsLeptin 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.

KeywordsAdipocytes Drotrecogin alpha activated Leptin mRNA Sepsis Supernatants AbbreviationsAPACHE IIAcute Physiology and Chronic Health Evaluation II

aPTTActivated partial thromboplastin time

AT IIIAntithrombin III

BMIBody mass index

CRPC-reactive protein CRP

CVDCentral venous pressure

DAADrotrecogin alpha activated

ELISAEnzyme-Linked Immunosorbent Assay

ICUIntensive care unit

INRInternational normalized ratio

LPSLipopolysaccheride

mRNAMessenger ribonucleic acid

qPCRQuantitative polymerase chain reaction

SDStandard deviation

SEMStandard error of mean

TNF alphaTumor necrosis factor alpha.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2334-12-217 contains supplementary material, which is available to authorized users.

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Autor: Michael Behnes - Martina Brueckmann - Siegfried Lang - Christian Putensen - Joachim Saur - Martin Borggrefe - Ursula Hoffma

Fuente: https://link.springer.com/



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