Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis
Détails
Etat: Public
Version: Final published version
Licence: Non spécifiée
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
ID Serval
serval:BIB_DA8F91A4048C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis
Périodique
Clinical Infectious Diseases
ISSN
1537-6591 (Electronic)
Statut éditorial
Publié
Date de publication
2007
Volume
44
Numéro
10
Pages
1321-1328
Langue
anglais
Résumé
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.
Mots-clé
Adolescent Adrenocorticotropic Hormone/*blood Adult Aged Bacteremia/*blood/microbiology Child Child, Preschool Cohort Studies Female Gram-Negative Bacterial Infections/*blood Humans Hydrocortisone/*blood Hypothalamo-Hypophyseal System/physiopathology Infant Macrophage Migration-Inhibitory Factors/*blood Male Meningitis, Meningococcal/blood Middle Aged Neisseria meningitidis Pituitary-Adrenal System/physiopathology Prospective Studies
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 14:28
Dernière modification de la notice
14/02/2022 8:57