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-α 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.

Keywords

Cytokine endotoxemia human lipopolysaccharide prehydration

References

Morimoto A. , Murakami N. , Ono T. , Watanabe T. Dehydration enhances endotoxin fever by increased production of endogenous pyrogen. Am J Physiol 1986; 251: R41—R47.

Rhee P. , Wang D. , Ruff P. et al. Human neutrophil activation and increased adhesion by various resuscitation fluids. Crit Care Med 2000; 28: 74—78.

Oreopoulos GD , Bradwell S. , Lu Z. et al. Synergistic induction of IL-10 by hypertonic saline solution and lipopolysaccharides in murine peritoneal macrophages. Surgery 2001; 130: 157—165.

van Eijk LT , Pickkers P. , Smits P. , van den BW , Bouw MP , van der Hoeven JG Microvascular permeability during experimental human endotoxemia: an open intervention study. Crit Care 2005; 9: R157—R164.

Leslie SJ , Attina T. , Hultsch E. et al. Comparison of two plethysmography systems in assessment of forearm blood flow. J Appl Physiol 2004; 96: 1794—1799.

Christ F. , Bauer A. , Brugger D. , Niklas M. , Gartside IB , Gamble J. Description and validation of a novel liquid metal-free device for venous congestion plethysmography. J Appl Physiol 2000; 89: 1577—1583.

Prabhakar U. , Eirikis E. , Davis HM Simultaneous quantification of proinflammatory cytokines in human plasma using the LabMAP assay. J Immunol Methods 2002; 260: 207—218.

Oliveira RP , Weingartner R. , Ribas EO , Moraes RS , Friedman G. Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis. Intensive Care Med 2002; 28: 1574—1581.

Hannemann L. , Reinhart K. , Korell R. , Spies C. , Bredle DL Hypertonic saline in stabilized hyperdynamic sepsis. Shock 1996; 5: 130—134.

10.

Rizoli SB , Kapus A. , Parodo J. , Fan J. , Rotstein OD Hypertonic immunomodulation is reversible and accompanied by changes in CD11b expression. J Surg Res 1999; 83: 130—13 5.

11.

Pascual JL , Ferri LE , Seely AJ et al. Hypertonic saline resuscitation of hemorrhagic shock diminishes neutrophil rolling and adherence to endothelium and reduces in vivo vascular leakage. Ann Surg 2002; 236: 634—642.

12.

Miyoshi M. , Nagata K. , Imoto T. , Goto O. , Ishida A. , Watanabe T. ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats. Am J Physiol 2003; 284: R1092—R1097.

13.

Watanabe T. , Hashimoto M. , Wada M. et al. Angiotensin-converting enzyme inhibitor inhibits dehydration-enhanced fever induced by endotoxin in rats. Am J Physiol 2000; 279: R1512—R1516.

14.

Graninger M. , Marsik C. , Dukic T. , Wagner OF , Blann AD , Jilma B. Enalapril does not alter adhesion molecule levels in human endotoxemia. Shock 2003; 19: 448—451.

15.

van der PT , Coyle SM , Barbosa K. , Braxton CC , Lowry SF Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 1996; 97: 713—719.

16.

Le Tulzo Y. , Shenkar R. , Kaneko D. et al. Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression. J Clin Invest 1997 ; 99: 1516—1524.

17.

Spengler RN , Allen RM , Remick DG , Strieter RM , Kunkel SL Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor. J Immunol 1990; 145: 1430—1434.

18.

Rivers E. , Nguyen B. , Havstad S. et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368—1377.

19.

Shoemaker WC , Appel PL , Kram HB , Waxman K. , Lee TS Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 1988; 94: 1176—1186.

20.

Berlauk JF , Abrams JH , Gilmour IJ , O'Connor SR , Knighton DR , Cerra FB Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg 1991; 214: 289—297.

21.

Annane D. , Bellissant E. , Cavaillon JM Septic shock. Lancet 2005; 365: 63—78.

22.

van Eijk LT , Pickkers P. , Smits P. , Bouw MP , van der Hoeven JG Severe vagal response after endotoxin administration in humans. Intensive Care Med 2004; 30: 2279—2281.