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Intensive Care Medicine

, Volume 29, Issue 9, pp 1456–1463 | Cite as

Modulation of host defense by hydrocortisone in stress doses during endotoxemia

  • Axel R. HellerEmail author
  • Susanne C. Heller
  • Annette Borkenstein
  • Sebastian N. Stehr
  • Thea Koch
Original

Abstract

Objective

To investigate the effects of low-dose hydrocortisone (HC) on neutrophil respiratory burst, phagocytosis, and elimination of E. coli from blood and tissue under endotoxemic and non-endotoxemic conditions.

Design

Randomized, controlled trial.

Setting

Experimental laboratory, university hospital.

Subjects

Forty-eight female chinchilla rabbits (n=8 in six groups A–F).

Interventions

In order to quantify the bacterial clearance process, defined numbers [108 colony forming units (CFU)] of Escherichia coli were injected intravenously into all anesthetized rabbits. Group A did not receive further intervention. Group B received bolus administration of HC 1.4 mg/kg and group C 14 mg/kg. Endotoxin (LPS, 40 μg/kg/h) was given to groups D, E, and F. Group E received additional bolus administration of HC 1.4 mg/kg and group F 14 mg/kg. All HC groups (B, C, E, and F) were continuously infused with HC 0.18 mg/kg/h.

Measurements

Monitored parameters were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, serum lactate and LPS concentrations, as well as nitrite and nitrate levels. Tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts.

Main results

In controls HC significantly delayed elimination of injected E. coli from the blood (P<0.01). LPS also prolonged bacterial elimination but additional HC did not further delay removal of E. coli from the blood. Under endotoxemia HC depressed respiratory burst, whereas phagocytosis functions remained unaltered. Moreover, bacterial colonization of organs was reduced after HC in the LPS groups. Significance, however, was reached only in the liver (P<0.05). Due to HC, clearance from LPS (P<0.01) and lactate (P<0.05) were improved. Levels of nitrite and nitrate did not differ among the groups.

Conclusion

HC demonstrated immunomodulatory effects even in stress doses. In endotoxemic states use of low-dose HC seems to be favorable, although not in non-septic conditions.

Keywords

Hydrocortisone Respiratory burst Phagocytosis Neutrophils Bacterial killing Sepsis 

Notes

Acknowledgments

The authors thank Dr. Renate Urbaschek, Birgit Kaschta, and Sylvia Thuy (Institute of Med. Microbiology and Hygiene), Kerstin Salomon, Jutta Schulte, Angelika Tapper, Monika Lehmer (Institute of Anesthesiology), and Jutta Christophel (Center of Med. Research, University Hospital of Mannheim, Germany) for excellent technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft (DFG, KO1814/2-1) and the Research Fund of the Faculty of Clinical Medicine Mannheim, University of Heidelberg.

References

  1. 1.
    Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ Jr (1995) Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23:1430–1439PubMedGoogle Scholar
  2. 2.
    Koo DJ, Jackman D, Chaudry IH, Wang P (2001) Adrenal insuficiency during the late stage of polymicrobial sepsis. Crit Care Med 29:618–622PubMedGoogle Scholar
  3. 3.
    Briegel J, Forst H, Hellinger H, Haller M (1991) Contribution of cortisol deficiency to septic shock. Lancet 338:507–508Google Scholar
  4. 4.
    Briegel J, Kellermann W, Forst H, Haller M, Bittl M, Hoffmann GE, Büchler M, Uhl W, Peter K (1994) Phospholipase A2 Study Group: low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. Clin Invest 72:782–787PubMedGoogle Scholar
  5. 5.
    Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K (1999) Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 27:723–732PubMedGoogle Scholar
  6. 6.
    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low-doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871PubMedGoogle Scholar
  7. 7.
    Cooper MS, Stewart PM (2003) Corticosteroid insufficiency in acutely ill patients. N Engl J Med 348:727–734CrossRefPubMedGoogle Scholar
  8. 8.
    Barnes PJ (1996) Mechanisms of action of glucocorticoids in asthma. Am J Respir Crit Care Med 154:21–27Google Scholar
  9. 9.
    Kawamura T, Inada I, Nara N, Wakusawa R, Endo S (1999) Influence of methylprednisolone on cytokine balance during cardiac surgery. Crit Care Med 27:545–548PubMedGoogle Scholar
  10. 10.
    Keh D, Boehnke T, Weber-Carstens S, Schulz C, Ahlers O, Bercker S, Volk HD, Doecke WD, Falke KJ, Gerlach H (2002) Immunological and hemodynamic effects of 'low-dose' hydrocortisone in septic shock. Am J Respir Crit Care Med 167:512–520CrossRefGoogle Scholar
  11. 11.
    Heller S, Weber K, Heller A, Urbaschek R, Koch T (1999) Pentoxifylline improves bacterial-clearance in hemorrhage and endotoxemia. Crit Care Med 27:756–763PubMedGoogle Scholar
  12. 12.
    Heller A, Schmeck J, Heller S, Phan H, Nebe T, Urbaschek R, KochT (2000) Endothelin-1 impairs PMN-respiratory burst and elimination of E. coli in rabbits. Crit Care Med 28:1515–1521PubMedGoogle Scholar
  13. 13.
    Lauer T, Kleinbongard P, Kelm M (2002) Indexes of NO bioavailability in human blood. News Physiol Sci 17:251–255PubMedGoogle Scholar
  14. 14.
    Sandys GH (1960) A new method of preventing swarming of Proteus sp. with a description of a new medium suitable for use in routine laboratory practice. J Med Lab Technol 17:224–233Google Scholar
  15. 15.
    Ditter B, Becker KP, Urbaschek R, Urbaschek B (1982) Detection of endotoxin in blood and other specimens by evaluation of photometrically registered LAL-reaction-kinetics in microtiter plates. Prog Clin Biol Res 93:385–392PubMedGoogle Scholar
  16. 16.
    Green LC, Wagner DA, Glogowski J (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Annal Biochem 126:131–138Google Scholar
  17. 17.
    Hume DA, Ross IL, Himes SR, Sasmono RT, Wells CA, Ravasi T (2002) The mononuclear phagocyte system revisited. J Leukoc Biol 72:621–627PubMedGoogle Scholar
  18. 18.
    Dandona P, Suri M, Hamouda W, Aljada A, Kumbkarni Y, Thusu K (1999) Hydrocortisone-induced inhibition of reactive oxygen species by polymorphonuclear neutrophils. Crit Care Med 27:2442–2444PubMedGoogle Scholar
  19. 19.
    Vicente-Manzanares M, Sancho D, Yanez-Mo M, Sanchez-Madrid F (2002) The leukocyte cytoskeleton in cell migration and immune interactions. Int Rev Cytol. 216:233–289Google Scholar
  20. 20.
    Morel F, Doussiere J, Vignais PV (1991) The superoxide-generating oxidase of phagocytic cells. Physiological, molecular and pathological aspects. Eur J Biochem 201:523–46PubMedGoogle Scholar
  21. 21.
    Pacelli R, Wink DA, Cook JA, Krishna MC, DeGraff W, Friedman N, Tsokos M, Samuni A, Mitchell JB (1995) Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli. J Exp Med 182:1469–1479PubMedGoogle Scholar
  22. 22.
    Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342:1334–1349PubMedGoogle Scholar
  23. 23.
    Pfeiffer L, Ehrhardt N, Kretzschmar M, Urbaschek R, Schubert K, Schirrmeister W (1996) Endotoxinämie und Multiorganversagen nach Polytrauma. Anaesthesiol Reanimat 21:91–96Google Scholar
  24. 24.
    Nockher WA, Scherberich JE (1997) Expression and release of the monocyte lipopolysachharide receptor antigen CD14 are suppressed by glucocoricoids in vivo and in vitro. J Immunol 158:1345–1352PubMedGoogle Scholar
  25. 25.
    Nakano T, Ohara O, Teraoka H, Arita H (1990) Glucocorticoids suppress group II phospholipase A2 production by blocking mRNA synthesis and post-transcriptional expression. J Biol Chem 265:12745–12748PubMedGoogle Scholar
  26. 26.
    Mitchell JA, Belvisi MG, Akarasereemom P, Robbins RA, Kwon OJ, Croxtall J, Barnes PJ, Vane JR (1994) Induction of cyclooxygenase-2 by cytokines in human epithelial cells: regulation by desxamethasone. Br J Pharmacol 113:1008–1014PubMedGoogle Scholar
  27. 27.
    Vittori E, Marini M, Fasoli A (1992) Increased expression of endothelin in bronchial endothelial cells of asthmatic patients and effects of corticosteroids. Am Rev Respir Dis 146:1320–1325PubMedGoogle Scholar
  28. 28.
    Walker BR, Williams BC (1992) Corticosteroids and vascular tone: mapping the messenger maze. Clin Sci (Lond) 82:597–605Google Scholar
  29. 29.
    Barnes PJ (1995) Beta-adrenergic receptors and their regulation: state of the art. Am J Respir Crit Care Med 152:838–860PubMedGoogle Scholar
  30. 30.
    Radomski MW, Palmer RMJ, Moncada S (1990) Glucocorticoids inhibit the expression of an inducible, but not the constitute nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047PubMedGoogle Scholar
  31. 31.
    Xie QW, Kashiwarbara Y, Nathan C (1994) Role of transcription Factor NF-κB/Rel in induction of nitric oxide synthase. J Biol Chem 269:4705–4708PubMedGoogle Scholar
  32. 32.
    Matejovic M, Radermacher P, Tugtekin I, Stehr A, Theisen M, Vogt J, Wachter U, Ploner F, Georgieff M, Trager K (2001) Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia. Shock 16:203–210PubMedGoogle Scholar
  33. 33.
    Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M (2001) Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci USA 98:12814–12819CrossRefPubMedGoogle Scholar
  34. 34.
    Pastor CM, Hadengue A, Nüssler AK (2000) Minor involvement of nitric oxide during chronic endotoxemia in anesthetized pigs. Am J Physiol Gastrointest Liver Physiol 278:G416–G424PubMedGoogle Scholar
  35. 35.
    Antonetti DA, Wolpert EB, DeMaio L, Harhaj NS, Scaduto RC Jr (2002) Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 80:667–677CrossRefPubMedGoogle Scholar
  36. 36.
    Schulz-Baldes A, Berger S, Grahammer F, Warth R, Goldschmidt I, Peters J, Schutz G, Greger R, Bleich M (2001) Induction of the epithelial Na+ channel via glucocorticoids in mineralocorticoid receptor knockout mice. Pflugers Arch 443:297–305CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Axel R. Heller
    • 1
    Email author
  • Susanne C. Heller
    • 1
  • Annette Borkenstein
    • 2
  • Sebastian N. Stehr
    • 1
  • Thea Koch
    • 1
  1. 1.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital Carl Gustav CarusDresdenGermany
  2. 2.Institute of Medical Microbiology and HygieneUniversity Hospital MannheimGermany

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