Journal Article

Association between High Levels of Blood Macrophage Migration Inhibitory Factor, Inappropriate Adrenal Response, and Early Death in Patients with Severe Sepsis

Marieke Emonts, Fred C. G. J. Sweep, Nicolai Grebenchtchikov, Anneke Geurts-Moespot, Marlies Knaup, Anne Laure Chanson, Veronique Erard, Pascal Renner, Peter W. M. Hermans, Jan A. Hazelzet and Thierry Calandra

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 44, issue 10, pages 1321-1328
Published in print May 2007 | ISSN: 1058-4838
Published online May 2007 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/514344
Association between High Levels of Blood Macrophage Migration Inhibitory Factor, Inappropriate Adrenal Response, and Early Death in Patients with Severe Sepsis

More Like This

Show all results sharing these subjects:

  • Infectious Diseases
  • Immunology
  • Public Health and Epidemiology
  • Microbiology

GO

Show Summary Details

Preview

Background.Identification of new therapeutic targets remains an imperative goal to improve the morbidity and mortality associated with severe sepsis and septic shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, has recently emerged as a critical mediator of innate immunity and experimental sepsis, and it is an attractive new target for the treatment of sepsis.

Methods.Circulating concentrations of MIF were measured in 2 clinical trial cohorts of 145 pediatric and adult patients who had severe sepsis or septic shock caused predominantly by infection with Neisseria meningitidis or other gram-negative bacteria, to study the kinetics of MIF during sepsis, to analyze the interplay between MIF and other mediators of sepsis or stress hormones (adrenocorticotropic hormone and cortisol), and to determine whether MIF is associated with patient outcome.

Results.Circulating concentrations of MIF were markedly elevated in 96% of children and adults who had severe sepsis or septic shock, and they remained elevated for several days. MIF levels were correlated with sepsis severity scores, presence of shock, disseminated intravascular coagulation, urine output, blood pH, and lactate and cytokine levels. High levels of MIF were associated with a rapidly fatal outcome. Moreover, in meningococcal sepsis, concentrations of MIF were positively correlated with adrenocorticotropic hormone levels and negatively correlated with cortisol levels and the cortisol : adrenocorticotropic hormone ratio, suggesting an inappropriate adrenal response to sepsis.

Conclusions.MIF is markedly and persistently up-regulated in children and adults with gram-negative sepsis and is associated with parameters of disease severity, with dysregulated pituitary-adrenal function in meningococcal sepsis, and with early death.

Journal Article.  4877 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.