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1 January 2005

Volume 191, Number 1
The Journal of Infectious Diseases 2005;191:138–144
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19101-0021$15.00
DOI: 10.1086/426401
MAJOR ARTICLE

Corticoids Normalize Leukocyte Production of Macrophage Migration Inhibitory Factor in Septic Shock

Virginie Maxime,1,2

Catherine Fitting,1

Djillali Annane,2 and

Jean‐Marc Cavaillon2

1Unit Cytokines and Inflammation, Institut Pasteur, Paris, and 2Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique–Hôpitaux de Paris, Faculté de Médecine Paris Ile de France Ouest, Garches, France

Background.A regulatory loop between macrophage migration inhibitory factor (MIF) and glucocorticoids has been characterized in animal models. Renewed interest in glucocorticoid treatment for septic shock offers an opportunity to analyze this regulatory loop in humans.

Methods.We investigated the ex vivo release of MIF by peripheral blood mononuclear cells (PBMCs) sampled from glucocorticoid‐treated and ‐untreated patients with septic shock. Blood was obtained, before glucocorticoid treatment, and within the first day of treatment, from patients with septic shock who required treatment with moderate doses of hydrocortisone and fludrocortisone.

Results.PBMCs from patients contained significantly higher amounts of MIF than cells from healthy control subjects. In culture, spontaneous release of MIF and release induced by lipopolysaccharide (LPS), heat‐killed staphylococci, and red blood cell lysates were significantly higher in patients than in control subjects. PBMCs from patients treated with glucocorticoids showed a lower release of MIF in response to LPS, heat‐killed Escherichia coli, and peptidoglycan than did PBMCs from untreated patients and showed levels similar to PBMCs from healthy control subjects.

Conclusion.To our knowledge, MIF is the first proinflammatory cytokine in which ex vivo release by circulating cells is enhanced during sepsis. Glucocorticoid treatment normalized the release of MIF by circulating PBMCs from patients with septic shock.

Received 4 May 2004; accepted 9 July 2004; electronically published 30 November 2004.

Reprints or correspondence: Dr. Jean‐Marc Cavaillon, Unit Cytokines and Inflammation, Institut Pasteur, 28 rue Dr. Roux, 75015 Paris, France ().

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  • Financial support: Institut Pasteur.

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