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Human and experimental septic shock are characterized by depletion of lipid droplets in the adrenals

Andrea Polito| Geoffroy Lorin de la Grandmaison| Arnaud Mansart| Estelle Louiset| Hervé Lefebvre| Tarek Sharshar| Djillali Annane
Original
Volume 36, Issue 11 / November , 2010

Pages 1852 - 1858

Abstract

Rationale

Cholesteryl ester deficiency which results in adrenal lipid store depletion has been proposed as a potential mechanism of sepsis associated adrenal insufficiency.

Objective

We investigated histological abnormalities associated with sepsis in human and mice adrenals.

Methods

From January 2006 to 2008, seven patients who died of septic shock and seven patients with rapidly fatal nonseptic illness were included. Adrenals were sampled within 12 h from death. Adrenals were also taken from 13 lipopolysaccharide (LPS)-challenged mice, 5 cecal ligation and puncture (CLP) mice and 5 controls. We semi-quantitatively analysed intensity of inflammation, necrosis, haemorrhage and lipid depletion.

Measurements and main results

In patients, lipid depletion scores were significantly higher in septic shock than in controls (p = 0.011). In animals, lipid depletion was higher following LPS or CLP than in controls (p = 0.003). In adrenal cortex, in patients and not in animals, global scores for inflammation (p = 0.002), necrosis (p = 0.009) and haemorrhage (p = 0.009) were significantly higher in septic shock than in controls. Similarly, in zona fasciculata, in patients and not in animals, scores for inflammation (p = 0.007), necrosis (p = 0.023) and haemorrhage (p = 0.023) were significantly higher in septic shock than in controls.

Conclusions

This study shows that diffuse lipid depletion in zona fasciculata is a hallmark of human septic shock, experimental endotoxaemia and sepsis. In patients, sepsis was associated with inflammation, necrosis and haemorrhage predominantly in zona fasciculata.

Keywords

References

  1. Polito A, Aboab J, Annane D (2007) The hypothalamic pituitary adrenal axis in sepsis. Novartis Found Symp 280:182–199
    • View reference on publisher's website
    • View reference on PubMed
  2. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M, American College of Critical Care Medicine (2008) Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 36:1937–1949
    • View reference on publisher's website
    • View reference on PubMed
  3. Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P (2003) Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med 174:1319–1326
    • View reference on publisher's website
  4. Prigent H, Maxime V, Annane D (2004) Science review: mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids. Crit Care 8:243–252
    • View reference on publisher's website
    • View reference on PubMed
  5. Mason JI, Rainey WE (1987) Steroidogenesis in the human fetal adrenal: a role for cholesterol synthesized de novo. J Clin Endocrinol Metab 64:140–147
    • View reference on publisher's website
    • View reference on PubMed
  6. Borkowski A, Delcroix C, Levin S (1972) Metabolism of adrenal cholesterol in man. I. In vivo studies. J Clin Invest 51:1664–1678
    • View reference on publisher's website
    • View reference on PubMed
  7. Borkowski A, Delcroix C, Levin S (1972) Metabolism of adrenal cholesterol in man. II. In vitro studies including a comparison of adrenal cholesterol synthesis with the synthesis of the clucocorticosteroid hormones. J Clin Invest 51:1679–1687
    • View reference on publisher's website
    • View reference on PubMed
  8. van Leeuwen HJ, Heezius EC, Dallinga GM, van Strijp JA, Verhoef J, van Kessel KP (2003) Lipoprotein metabolism in patients with severe sepsis. Crit Care Med 31:1359–1366
    • View reference on publisher's website
    • View reference on PubMed
  9. Temel RE, Trigatti B, DeMattos RB, Azhar S, Krieger M, Williams DL (1997) Scavenger receptor class B, type I (SR-BI) is the major route for the delivery of high density lipoprotein cholesterol to the steroidogenic pathway in cultured mouse adrenocortical cells. Proc Natl Acad Sci USA 94:13600–13605
    • View reference on publisher's website
    • View reference on PubMed
  10. Cai L, Ji A, de Beer FC, Tannock LR, van der Westhuyzen DR (2008) SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance. J Clin Invest 118:364–375
    • View reference on publisher's website
    • View reference on PubMed
  11. Hoekstra M, Meurs I, Koenders M, Out R, Hildebrand RB, Kruijt JK, Van Eck M, Van Berkel TJ (2008) Absence of HDL cholesteryl ester uptake in mice via SR-BI impairs an adequate adrenal glucocorticoid-mediated stress response to fasting. J Lipid Res 49:738–745
    • View reference on publisher's website
    • View reference on PubMed
  12. American College of Chest Physicians/Society of Critical Care Medicine (1992) Consensus Conference: definitions for sepsis and multiple organ failure, and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874
    • View reference on publisher's website
  13. Wichterman KA, Baue AE, Chaudry IH (1980) Sepsis and septic shock—a review of laboratory models and a proposal. J Surg Res 29:189–201
    • View reference on publisher's website
    • View reference on PubMed
  14. Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPSII) based on a European/North American multicenter study. JAMA 270:2957–2963
    • View reference on publisher's website
    • View reference on PubMed
  15. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710
  16. Movat HZ (1955) Demonstration of all connective tissue elements in a single section. Arch Pathol 60:289–295
  17. Gurr G (1953) A practical manual of medical and biological stain technics. Interscience, New York, p 65
  18. Mowry RW (1956) Alcian blue technics for the histochemical study of acidic carbohydrates. J Histochem Cytochem 4:407
  19. Chiffelle TL, Putt FA (1951) Propylene and ethylene glycol as solvents for Sudan IV and Sudan Black B. Stain Technol 26:51–56
    • View reference on PubMed
  20. Weber AFM, Philipps MG, Bell JT (1956) An improved method fort he Schultz cholesterol test. J Histochem Cytochem 4:308–309
    • View reference on PubMed
  21. Sharshar T, Gray F, Lorin de la Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, Orlikowski D, Raphael JC, Gajdos P, Annane D (2003) Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 362:1799–1805
    • View reference on publisher's website
    • View reference on PubMed
  22. Melby JC, Spink WW (1958) Comparative studies on adrenal cortical function and cortisol metabolism in healthy adults and in patients with shock due to infection. J Clin Invest 37:1791–1798
    • View reference on publisher's website
    • View reference on PubMed
  23. Arlt W, Hammer F, Sanning P, Butcher SK, Lord JM, Allolio B, Annane D, Stewart PM (2006) Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock. J Clin Endocrinol Metab 91:2548–2554
    • View reference on publisher's website
    • View reference on PubMed
  24. Lichtarowicz-Krynska EJ, Cole TJ, Camacho-Hubner C, Britto J, Levin M, Klein N, Aynsley-Green A (2004) Circulating aldosterone levels are unexpectedly low in children with acute meningococcal disease. J Clin Endocrinol Metab 89:1410–1414
    • View reference on publisher's website
    • View reference on PubMed
  25. du Cheyron D, Lesage A, Daubin C, Ramakers M, Charbonneau P (2003) Hyperreninemic hypoaldosteronism: a possible etiological factor of septic shock-induced acute renal failure. Intensive Care Med 29:1703–1709

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