TY  - EJOU
AU  - Jilma-Stohlawetz, Petra 
AU  - Kliegel, Tuende 
AU  - Kantner-Schlifke, Irene 
AU  - Strasser-Marsik, Claudia 
AU  - Mayr, Florian B. 
AU  - Jilma, Bernd 

TI  - Upregulation of cytokine mRNA in circulating leukocytes during human endotoxemia
T2  - European Cytokine Network

PY  - 2017
VL  - 28
IS  - 1
SN  - 1952-4005

AB  - Background: Endotoxemia induces pronounced changes in leukocyte count and enhances the release
of many cytokines. However, the molecular regulation of this cytokine release is poorly characterized in humans.
Methods: The time course of mRNA expression of 24 cytokines in circulating leukocytes was studied in a wellstandardized
model of human endotoxemia (2 ng/kg). Real-time polymerase chain reaction (RT-PCR) was used
to quantify the lipopolysaccharide (LPS)-inducible mRNA levels of leukocytes from 16 healthy volunteers in a
randomized, placebo-controlled trial. Results: Baseline mRNA levels of interleukins including IL-1α, IL-3, IL-5,
IL-6, IL-12p40, IL-13, IL-15, IL-17, granulocyte colony-stimulating factor (G-CSF) and granulocyte monocyte
CSF (GM-CSF) were below detectable levels in normal blood of the healthy participants. After 2 h, LPS infusion
increased median mRNA levels of IL-1α by >1100-fold and IL-1β and IL-8 by 33-fold and 46-fold, respectively.
In contrast, levels of tumor necrosis factor (TNF-α) and IL-10 mRNA increased by only 7-fold, whereas changes
in mRNA expression of other cytokines showed either a more than two fold increase or were undetectable. In vitro
incubation of whole blood with 50 pg/mL LPS for 2 h enhanced transcription levels of IL-1α mRNA by >10,000-
fold, IL-6 and IL-12p40 by >1000-fold, IL-1β by 400-fold, TNF-α by 100-fold, IL-8, IL-18, interferon γ (IFN-γ)
and G-CSF by >10-25-fold, and IL-10, IL-12p35, TNF-β, and IL-13 by 10-25-fold. Conclusion: Only half of the 24
evaluated cytokines were expressed at the mRNA level in circulating leukocytes under basal conditions and after an
LPS challenge. Only IL-1α, IL-1β, IL-10, IL-8, and TNF-α were upregulated in the circulating leukocytes, whereas
several other cytokines (including IL-6 and G-CSF), were expressed on the mRNA level following in vitro incubation
of blood with LPS. In addition, IL-1α and IL-1β might be potential diagnostic targets in inflammatory diseases.
KW  - randomized controlled trial
KW  -  endotoxemia
KW  -  mRNA
KW  -  cytokines
KW  -  RT-PCR

DO  - 10.1684/ecn.2017.0389