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Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome

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Abstract

There is increasing evidence that the hypercortisolemia in inflammatory diseases suppresses the elaboration of proinflammatory cytokines, thus protecting the host from its own defence reactions. In severe sepsis and septic shock cortisol levels are usually elevated, but some patients may have relative adrenal insufficiency. This may contribute to the overwhelming systemic inflammatory response syndrome. We evaluated the impact of low-dose hydrocortisone infusion (10 mg/h) on the course of the systemic inflammatory response syndrome. This dose corresponds to a maximum secretory rate of cortisol achieved in corticotropin-stimulated healthy humans. In a prospective observational study 57 surgical patients with severe sepsis or septic shock were studied, of which in addition to the conventional treatment 12 patients were infused with low-dose hydrocortisone, and 45 were treated without any corticosteroid. In the longitudinal analysis the systemic inflammatory response — as judged by body temperature, cardiovascular response, and kinetics of inflammatory mediators such as phospholipase A2, C-reactive protein, and neutrophil elastase — started to differ in favor of the hydrocortisone-treated patients after 2 days of treatment (P < 0.05, Mann-Whitney U test). The difference disappeared after withdrawal of exogenous cortisol. Shock reversal was achieved in all patients treated with low-dose hydrocortisone. The data provide evidence that low-dose hydrocortisone infusion attenuates the systemic inflammatory response in human septic shock. From an immunological point of view a relative cortisol deficiency may contribute to the amplified immune response in systemic inflammatory diseases. A randomized clinical trial must clarify the impact of low-dose hydrocortisone infusion on the clinical course and outcome of septic shock patients.

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Abbreviations

TNF:

Tumor necrosis factor

PLA2 :

phospholipase A2

CRP:

C-reactive protein

E-PI:

neutrophil elastase-α1-proteinase inhibitor complex

IL:

interleukin

References

  1. Barber AE, Coyle SM, Fong Y, Fischer E, Marano MA, Calvano SE, Moldawer LL, Shires T, Lowry SF (1990) Impact of hypercortisolemia on the metabolic and hormonal responses to endotoxin in humans. Surg Forum 41:74–77

    Google Scholar 

  2. Barber AE, Coyle SM, Marano MA, Fischer E, Calvano SE, Fong Y, Moldawer LL, Lowry SF (1993) Glucocorticoid therapy alters hormonal and cytokine response to endotoxin in man. J Immunol 150:1999–2006

    Google Scholar 

  3. Billiau A, Vandekerckhove F (1991) Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock. Eur J Clin Invest 21:559–573

    Google Scholar 

  4. Bone RC, Fisher CJ, Clemmer TP, Slotman GJ, Metz CA, Balk RA, the Methylprednisolone Severe Sepsis Study Group (1987) A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317:653–658

    Google Scholar 

  5. Briegel J, Forst H, Hellinger H, Haller M (1991) Contribution of cortisol deficiency to septic shock. Lancet 338:507–508

    Google Scholar 

  6. Dawson-Saunders B, Trapp RG (1990) Estimating & comparing means. In: Basic and clinical biostatistics. Appleton & Lange, San Mateo Norwalk, pp 99–123

    Google Scholar 

  7. Dinarello CA, Wolff SM (1990) Pathogenesis of fever. In: Mandell GL, Douglas RG, Bennett JE (eds) Infectious diseases. Churchill Livingstone, New York Edinburgh London, pp 462–467

    Google Scholar 

  8. Duswald K-H, Jochum M, Schramm W, Fritz H (1985) Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery. Surgery 98:892–899

    Google Scholar 

  9. Elebute EA, Stoner HB (1983) The grading of sepsis. Br J Surg 70:29–31

    Google Scholar 

  10. Finlay WEI, McKee JI (1982) Serum cortisol levels in severely stressed patients. Lancet 1:1414–1415

    Google Scholar 

  11. Goulding NJ, Guyre PM (1993) Glucocorticoids, lipocortins and the immune response. Curr Opin Immunol 5:108–113

    Google Scholar 

  12. Hoffmann GE, Neumann U (1989) Modified photometric method for the determination of phospholipase A activities. Klin Wochenschr 67:106–109

    Google Scholar 

  13. Lin L-L, Lin AY, Knopf JL (1992) Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid. Proc Natl Acad Sci USA 89:6147–6151

    Google Scholar 

  14. Munck A, Guyre PM, Holbrook NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5:25–44

    Google Scholar 

  15. Peers SH, Smillie F, Elderfield AJ, Flower RJ (1993) Glucocorticoid-and non-glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo. Br J Pharmacol 108:66–72

    Google Scholar 

  16. Pruzanski W, Vadas P (1991) Phospholipase A2 — a mediator between proximal and distal effectors of inflammation. Immunology Today 12:143–146

    Google Scholar 

  17. Pruzanski W, Stefanski E, Wilmore DW, Martich GD, Hoffman AGD, Suffredini AF, Vadas P (1990) Sequential activation of TNF-phospholipase A2 axis following i.v. endotoxin challenge in human vounteers. FASEB J 4:A1714

    Google Scholar 

  18. Redl H, Schlag G, Schiesser A, Davies J (1993) Tumor necrosis factor is a mediator of phospholipase release during bacteremia in baboons. Am J Physiol Heart Circ Physiol 264:H2119-H2123

    Google Scholar 

  19. Rees AJ, Lockwood CM (1993) Immunosuppressive drugs in clinical practice. In: Lachmann PJ, Peters K, Rosen FS, Walport MJ (eds) Clinical aspects of immunology. Blackwell, London, pp 929–969

    Google Scholar 

  20. Rothwell PW, Udwadia ZF, Lawler PG (1991) Cortisol response to corticotropin and survival in septic shock. Lancet 337:582–583

    Google Scholar 

  21. Santos AA, Scheltinga MR, Lynch E, Brown EF, Lawton P, Chambers E, Browning J, Dinarello CA,Wolff SM, Wilmore DW (1993) Elaboration of interleukin 1-receptor antagonist is not attenuated by glucocorticoids after endotoxemia. Arch Surg 128:138–144

    Google Scholar 

  22. Schneider AJ, Voerman HJ (1991) Abrupt hemodynamic improvement in late septic shock with physiological doses of glucocorticoids. Intensive Care Med 17:436–437

    Google Scholar 

  23. Spinas GA, Bloesch D, Keller U, Zimmerli W, Cammisuli S (1991) Pretreatment with ibuprofen augments circulating tumor necrosis factor α, interleukin-6, and elastase during acute endotoxinemia. J Infect Dis 163:89–95

    Google Scholar 

  24. Sprung CL, Caralis PV, Marcial EH, Pierge M, Gelbard MA, Long WM, Duncan RC, Tendler MD, Karpf M (1984) The effects of high-dose corticosteroids in patients with septic shock. N Engl J Med 311:1137–1143

    Google Scholar 

  25. Thomas JP, El-Shaboury AH (1971) Aldosterone secretion in steroid-treated patients with adrenal suppression. Lancet 1:623–625

    Google Scholar 

  26. Vadas P, Pruzanski W, Stefanski E, Ruse J, Farewell V, McLaughlin J, Bombardier C (1988) Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study. J Lab Clin Med 111:584–590

    Google Scholar 

  27. Vadas P, Pruzanski W, Stefanski E, Sternby B, Mustard R, Bohnen J, Fraser I, Farewell V, Bombardier C (1988) Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse. Crit Care Med 16:1–7

    Google Scholar 

  28. Van den Bosch H, Schalkwijk C, Pfeilschifter J, Märki F (1992) The induction of cellular group II phospholipase A2 by cytokines and its prevention by dexamethasone. Adv Exp Med Biol 318:1–10

    Google Scholar 

  29. Veterans Administration Systemic Sepsis Cooperative Study Group (1987) Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 317:659–665

    Google Scholar 

  30. Waage A, Bakke O (1988) Glucocorticoids suppress the production of tumor necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology 63:299–302

    Google Scholar 

  31. Zuckerman SH, Shellhaas J, Butler LD (1989) Differential regulation of lipopolysaccharide-induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur J Immunol 19:301–305

    Google Scholar 

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Correspondence to: J. Briegel

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Briegel, J., Kellermann, W., Forst, H. et al. Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. Clin Investig 72, 782–787 (1994). https://doi.org/10.1007/BF00180547

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