Open Access

ARTICLE

IFN-γ is not induced through increased plasma concentrations of interleukin-12/interleukin-18 during human endotoxemia

Mirrin J. Dorresteijn^1,2,*, Peter Pickkers^1,2,*, Mihai G. Netea^3,4, Johannes G. Van der Hoeven^1,4

1 Department of Intensive Care Medicine (519), Radboud University Nijmegen Medical Center, PO-box 9101, 6500 HB, Nijmegen, The Netherlands
2 Department of Pharmacology-Toxicology
3 Department of Medicine
4 Nijmegen University Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

* Corresponding Author: P. Pickkers,

European Cytokine Network 2005, 16(3), 191-193.

Accepted 23 June 2005;

Abstract

Endotoxin administration to animals and humans is an accepted experimental model of Gramnegative 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-γ 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-γ axis. Seven healthy volunteers received E. coli endotoxin (O:113). Hemodynamics, temperature and the course of plasma concentrations of TNF-α, IL-1β, IL-12, IL-18 and IFN-γ were determined. Endotoxin administration resulted in the expected flu-like symptoms, a temperature of 38.8 ± 0.3℃ (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-a increased from 16.6 ± 8.2 to 927 ± 187 pg/mL (p < 0.003). IL-1b 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-γ 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-γ production in human endotoxemia.

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