Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis

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Serval ID
serval:BIB_DA8F91A4048C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis
Journal
Clinical Infectious Diseases
Author(s)
Emonts Marieke, Sweep Fred C.G.J., Grebenchtchikov Nicolai, Geurts-Moespot Anneke, Knaup Marlies, Chanson Anne Laure, Erard Veronique, Renner Pascal, Hermans Peter W. M., Hazelzet Jan A., Calandra Thierry
ISSN
1537-6591 (Electronic)
Publication state
Published
Issued date
2007
Volume
44
Number
10
Pages
1321-1328
Language
english
Abstract
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.
Keywords
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
Yes
Create date
25/01/2008 14:28
Last modification date
25/09/2019 7:10
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