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The Neuroendocrine Response to Sepsis

  • D. Annane

Abstract

Acute response to LPS includes the release of a number of proinflammatory mediators that reach the brain in areas free of blood-brain barrier, or via specific transport systems. The hypothalamic-pituitary axis is also activated via neural routes. Then, infection is characterized by high circulating levels of adrenocorticotrope hormone (ACTH), and cortisol which remain in plateau as long as the stressful condition is maintained. Circulating vasopressin levels follow a biphasic response with high concentrations, followed by relative vasopressin insufficiency in about one third of cases. Early response to sepsis is characterized by decreased serum T3 and increased rT3 levels. Serum T4 levels decrease within 24 to 48 h, and thyroid-stimulating (TSH) levels remain normal, and have no more circadian rhythm. Prolonged sepsis is associated with centrally induced hypothyroidism. In the initial response to sepsis, growth hormone levels are high with attenuated oscillatory activity and low insulin-like growth factor (IGF)-1 levels. Later on, growth hormone (GH) secretion shows a reduced pulsatil fraction, and correlates with low circulating levels of IGF-1. Exposure to endotoxin caused prompt increase in circulating adrenaline and noradrenaline concentrations. Catecholamines have a very short half-life and are metabolized through captation, enzymatic inactivation, or renal excretion. Plasma catecholamines levels remain elevated in plateau up to few months after recovery. Insulin levels rapidly increased following LPS as a result of both increased secretion and tissue resistance. The clinical consequences of the stress system activation include behavioral changes, cardiovascular, metabolic and immune adaptations.

Keywords

Growth Hormone Septic Shock Critical Illness Migration Inhibit Factor Adrenal Medulla 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Chrousos GP (2000) The stress response and immune function: Clinical implications. The 1999 Novera H. Spector Lecture. Ann NY Acad Sci 917:38–67PubMedGoogle Scholar
  2. 2.
    Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78CrossRefPubMedGoogle Scholar
  3. 3.
    McCann SM, Kimura M, Karanth S et al (2000) The mechanism of action of cytokines to control the release of hypothalamic and pituitary hormones in infection. Ann NY Acad Sci 917:4–18PubMedCrossRefGoogle Scholar
  4. 4.
    Koenig JI (1991) Presence of cytokines in the hypothalamic-pituitary axis. Prog Neuroendocrinoimmunol 4:143–153Google Scholar
  5. 5.
    Karanth S, Lyson K, McCann SM (1999) Effects of cholinergic agonists and antagonists on interleukin-2-induced corticotropin-releasing hormone release from the mediobasal hypothalamus. Neuroimmunomodulation 6:168–174CrossRefPubMedGoogle Scholar
  6. 6.
    Polito A, Annane D (2008) Adrenal glands/corticosteroids and multiple organ dysfunction syndrome. J Organ Dysfunc 4:(4)208–215CrossRefGoogle Scholar
  7. 7.
    Sharshar T, Gray F, Lorin de la Grandmaison G et al (2003) Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 362:1799–1805CrossRefPubMedGoogle Scholar
  8. 8.
    De Groot LJ (1999) Dangerous dogmas in medicine: The nonthyroidal illness syndrome. J Clin Endocrinol Metab 84:151–164CrossRefPubMedGoogle Scholar
  9. 9.
    Ross R, Miell J, Freeman E et al (1991) Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. Clin Endocrinol (Oxf) 35:47–54CrossRefGoogle Scholar
  10. 10.
    Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806CrossRefPubMedGoogle Scholar
  11. 11.
    Maier SF, Watkins LR (1998) Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behaviour, mood, and cognition. Psychol Rev 105:83–107CrossRefPubMedGoogle Scholar
  12. 12.
    Annane D, Trabold F, Sharshar T et al (1999) Inappropriate sympathetic activation at onset of septic shock: A spectral analysis approach. Am J Respir Crit Care Med 160:458–465PubMedGoogle Scholar
  13. 13.
    Godin PJ, Buchman TG (1996) Uncoupling of biological oscillators: A complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med 24:1107–1116CrossRefPubMedGoogle Scholar
  14. 14.
    Landry DW, Levin HR, Gallant EM et al (1997) Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 95:1122–1125PubMedGoogle Scholar
  15. 15.
    Minokoshi Y, Kahn CR, Kahn BB (2003) Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J Bio Chem 278:33609–33612CrossRefGoogle Scholar
  16. 16.
    Van den Berghe G (2004) How does blood glucose control with insulin save lives in intensive care? J Clin Invest 114(9):1187–1195PubMedGoogle Scholar
  17. 17.
    Annane D, Vignon P, Bollaert PE et al (2005) Norepinephrine plus dobutamine versus epinephrine alone for the management of septic shock. (Abstract). Intensive Care Med 31:S1–S18CrossRefGoogle Scholar
  18. 18.
    Annane D, Sebille V, Charpentier C et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871CrossRefPubMedGoogle Scholar
  19. 19.
    Sprung CL, Annane D, Keh D et al (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124CrossRefPubMedGoogle Scholar
  20. 20.
    Van den Berghe G, Wouters P, weekers F et al (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367CrossRefPubMedGoogle Scholar
  21. 21.
    Van den Berghe G, Wilmer A, Hermans G et al (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354:449–461CrossRefPubMedGoogle Scholar
  22. 22.
    Brunkhorst FM, Engel C, Bloos F et al (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139CrossRefPubMedGoogle Scholar
  23. 23.
    The NICE-SUGAR Investigators (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2009

Authors and Affiliations

  • D. Annane
    • 1
  1. 1.Service de Réanimation, Hôpital Raymond Poincaré (AP-HP)University of Versailles SQYGarchesFrance

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