TY  - JOUR
AU  - Dorresteijn, M.J.
AU  - Pickkers, P.
AU  - Netea, M.G.
AU  - Hoeven, J.G. van der
PY  - 2005
UR  - https://hdl.handle.net/2066/47341
AB  - Endotoxin administration to animals and humans is an accepted experimental model of Gram-negative sepsis, and endotoxin is believed to play a major role in triggering the activation of cytokines. In septic patients, the IL-12/IL-18/IFN-gamma axis is activated and correlates with mortality. Our aim was to investigate the effects of endotoxin administration in humans on the activation of the IL-12/IL-18/IFN-gamma axis. Seven healthy volunteers received E. coli endotoxin (O:113). Hemodynamics, temperature and the course of plasma concentrations of TNF-alpha, IL-1beta, IL-12, IL-18 and IFN-gamma were determined. Endotoxin administration resulted in the expected flu-like symptoms, a temperature of 38.8 +/- 0.3(o)C (p < 0.003), a decrease in mean arterial blood pressure of 14.8 +/- 1.8 mmHg (p < 0.0002) and an increase in heart rate of 27.5 +/- 4.8 bpm (p < 0.002) compared to baseline values. TNF-alpha increased from 16.6 +/- 8.2 to 927 +/- 187 pg/mL (p < 0.003). IL-1beta increased from 8.6 +/- 0.5 to 25.3 +/- 2.0 pg/mL (p < 0.0001). IL-12 showed no significant increase (8.2 +/- 0.2 to 9.3 +/- 0.8 pg/mL, p = 0.13), and all IL-18 measurements remained below the level of detection. In contrast, IFN-gamma showed an increase from 106.6 +/- 57.1 to 152.7 +/- 57.8 (p < 0.005). These results indicate that pathways other than the IL-12/IL-18 axis may induce IFN-gamma production in human endotoxemia.
TI  - IFN-gamma is not induced through increased plasma concentrations of interleukin-12/interleukin-18 during human endotoxemia.
EP  - 193
SN  - 1148-5493
IS  - iss. 3
SP  - 191
JF  - European Cytokine Network
VL  - vol. 16
ER  - 
TY  - JOUR
AU  - Dorresteijn, M.J.
AU  - Eijk, L.T.G.J. van
AU  - Netea, M.G.
AU  - Smits, P.
AU  - Hoeven, J.G. van der
AU  - Pickkers, P.
PY  - 2005
UR  - https://hdl.handle.net/2066/48621
AB  - Clinical experience suggests that the administration of fluids in human endotoxemia reduces symptoms. In the present study, the effects of a standardised fluid protocol on symptoms, inflammatory and hemodynamic parameters in human endotoxemia are determined. With approval of the local ethics committee, 16 healthy volunteers received 2 ng/kg of Escherichia coli endotoxin (O:113). After an overnight fast, nine subjects received 1.5 l of 2.5% glucose/0.45% NaCl the hour prior to the endotoxin administration and 150 ml/h during the course of the experiment ('prehydrated group'). Seven subjects only received a continuous infusion of 75 ml/h during the experiment ('non-prehydrated group'). The course of inflammatory parameters and symptoms were determined and mean arterial pressure, heart rate and forearm blood flow were measured. In the prehydrated group, TNF-alpha increased to 522 +/- 63 pg/ml (mean +/- SEM) while the maximum in the non-prehydrated group was 927 +/- 187 pg/ml (P < 0.04). IL-10 increased similarly in both groups (non-prehydrated 117 +/- 18 pg/ml and prehydrated 99 +/- 18 pg/ml; P = NS). The prehydrated group had a significantly lower (P < 0.004) symptom score and recovered sooner (P = 0.004). Endotoxin-induced changes in hemodynamics revealed no significant differences between groups. We demonstrate that prehydration in experimental human endotoxemia significantly shifts the cytokine balance towards a more anti-inflammatory pattern. This effect is associated with a reduction in symptoms, whereas the changes in hemodynamic parameters are not influenced by prehydration.
TI  - Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia.
EP  - 293
SN  - 0968-0519
IS  - iss. 5
SP  - 287
JF  - Journal of Endotoxin Research
VL  - vol. 11
DO  - https://doi.org/10.1179/096805105X58715
ER  -