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Effects of epinephrine and norepinephrine on endotoxin-induced tissue factor expression in blood monocytes

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Background

Tissue factor (TF) is the most important initiator of intravascular coagulation. In monocytes the expression of pro-inflammatory cytokines and TF is controlled by the same transcription factors. Catecholamines, frequently used in sepsis therapy of critically ill patients, have been shown to inhibit endotoxin-induced expression of monocyte cytokines, such as TNF-α or IL-6 [1]. The aim of our study was to prove whether epinephrine (EPI) and norepinephrine (NOREPI) may also affect TF expression.

Methods

To induce TF and TNF-α expression in monocytes we incubated citrated human whole blood (WB) for four hours with LPS (E. coli 055:B5; 50 ng/ml). TF expression on monocytes was determined by flow cytometry, TNF-α secretion was measured by ELISA.

Results

Incubating WB samples with 50 ng/ml LPS we observed an increase in the number of TF-positive monocytes from 3.9± 0.7% to 42.9± 2.8%. 5.5 nM EPI inhibited LPS-induced TF expression by about 16% (P=0.03), but the inhibitory effect was attenuated at higher EPI concentrations (>550 nM). LPS-induced TNF-α secretion (4.2± 0.5 ng/ml) was inhibited by about 60% in presence of 5.5 nM EPI, and maximum inhibition of 75% was reached at 55 nM. Compared to EPI, higher concentrations of NOREPI were needed to get a significant inhibition of monocyte activity. Inhibition of TF-expression by 13% was observed at 550 nM and the same inhibition was observed at 5,500 nM. TNF-α secretion was inhibited in a clear dose-dependent manner and amounted at 5.5 nM NOREPI to about 35% and at 5500 nM to about 75%.

Conclusion

EPI is more effective than NOREPI to inhibit LPS-induced monocyte TF expression and TNF-α secretion. At higher concentrations EPI also seemed to have a stimulatory effect on TF expression, which could be due to an interaction of EPI-activated platelets [2] with monocytes.

References

  1. 1.

    van der Poll , et al.: . Infect Immunol 1994, 62: 2046-2050.

  2. 2.

    Amirkhosravi , et al.: . Thromb Haemost 1996, 75: 87-95.

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Keywords

  • Tissue Factor
  • Tissue Factor Expression
  • Monocyte Activity
  • Whole Blood
  • Whole Blood Sample