Corticoids normalize leukocyte production of macrophage migration inhibitory factor in septic shock.
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.


CONCLUSIONS
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.
Maxime
Virginie
V
Unit Cytokines and Inflammation, Institut Pasteur, 75015 Paris, France.
Fitting
Catherine
C
Annane
Djillali
D
Cavaillon
Jean-Marc
JM
D000368:Aged; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D010457:Peptidoglycan / Q000276:immunology; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology*; D013210:Staphylococcus / Q000276:immunology
D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D010457:Peptidoglycan; D005438:Fludrocortisone; D006854:Hydrocortisone