Prehydration shifts the cytokine response towards a more anti-inflammatory balance during human endotoxemia

Introduction

Animal experiments have shown that dehydration significantly alters the effects of endotoxin administration. Clinical experience suggests that the administration of fluids in human endotoxemia causes an attenuation of symptoms. In the present study the effects of a standardised fluid protocol on symptoms, inflammatory and hemodynamic parameters in human endotoxemia are determined.

Methods

With approval of the local ethics committee, 16 healthy volunteers received 2 ng/kg Escherichia coli endotoxin (O:113). After an overnight fast, seven subjects only received a continuous infusion of 75 ml/hour glc2.5%/NaCl 0.45% solution during the experiment ('non-prehydrated group'), while nine subjects received 1.5 l the hour prior to the endotoxin administration and 150 ml/hour during the course of the experiment ('prehydrated group'). In order to determine the inflammatory effects of the endotoxin CRP, white blood cell count and cytokine concentrations were determined at different time points. The course of body temperature was determined and subjects were asked to score the severity of their symptoms. Mean arterial pressure and heart rate were measured.

Results

Prehydration reduced the inflammatory response after endotoxin administration. The induction of the proinflammatory cytokines (tumour necrosis factor alpha, IL-1β, IL-6, IL-8) was attenuated by the prehydration. The prehydrated group tumour necrosis factor alpha reached a peak value of 522 ± 63 pg/ml (mean ± standard error) compared with 927 ± 187 pg/ml in the non-prehydrated group (peak P = 0.04, analysis of variance [ANOVA] repeated measures P = 0.046). In contrast, the anti-inflammatory cytokine IL-10 demonstrated a trend towards higher values in the prehydrated group (prehydrated 117 ± 18 pg/ml and non-prehydrated 99 ± 18, P = not significant). The prehydrated group developed a significantly lower fever (38.1 versus 38.8°C in the non-prehydrated group, P < 0.05), scored significantly lower on their symptom score (ANOVA repeated measures, P = 0.036) and recovered sooner. Endotoxin administration induced a 15 ± 3% and 15 ± 1% fall in MAP and an increase in heart rate (54 ± 2% and 47 ± 3%) in the prehydrated and non-prehydrated group, respectively. Both revealed no significant differences between groups.

Conclusions

We demonstrate that prehydration significantly shifts the cytokine balance towards a more anti-inflammatory pattern in human endotoxemia. This effect is associated with a reduction in symptoms, whereas the changes in hemodynamic parameters are not influenced by prehydration. To correctly interpret the inflammatory effects of endotoxin in humans, the use of prehydration should be standardized.