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Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia

Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Lucas T. van Eijk

Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Mihai G. Netea

Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Nijmegen University Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Paul Smits

Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Johannes G. van der Hoeven

Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Nijmegen University Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Peter Pickkers

Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, p.pickkers{at}ic.umcn.nl

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- 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.

Key Words: Cytokine • endotoxemia • human • lipopolysaccharide • prehydration

Journal of Endotoxin Research, Vol. 11, No. 5, 287-293 (2005)
DOI: 10.1177/09680519050110050501


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