title: Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia.
abstract: 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.
authors.affiliation: Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Mirrin J
authors.initials: MJ
authors.lastname: Dorresteijn
authors.forename: Lucas T
authors.initials: LT
authors.lastname: van Eijk
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000328:Adult; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D019446:Endotoxemia / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D004926:Escherichia coli / Q000472:pathogenicity; D005260:Female; D005440:Fluid Therapy; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D012720:Severity of Illness Index; D014882:Water-Electrolyte Balance
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides