Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical trials (original) (raw)
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MACROPHAGE MIGRATION INHIBITORY FACTOR LEVELS CORRELATE WITH FATAL OUTCOME IN SEPSIS
Shock, 2004
Macrophage migration inhibitory factor (MIF) is a cytokine playing a critical role in the pathophysiology of experimental sepsis. The purpose of this study was to determine the levels of MIF and to compare those to interleukin-6 (IL-6) levels in predicting mortality among critically ill patients with sepsis. The levels of MIF and IL-6 were measured in 25 patients with septic shock, 17 patients with sepsis, and 11 healthy volunteers. The median plasma concentrations of MIF and IL-6 were significantly higher in patients with septic shock and in patients with sepsis than in healthy controls. MIF levels were significantly different between survivors and nonsurvivors, as were IL-6 levels. Discriminatory power in predicting mortality, as assessed by the areas under receiver operating characteristic curves (AUROC), was 0.793 for MIF and 0.680 for IL-6. Finally, high plasma levels of MIF (>1100 pg/mL) had a sensitivity of 100% and a specificity of 64% to identify the patients who eventually would evolve to a fatal outcome. Thus, our data suggest that an elevated MIF level in recently diagnosed septic patients appears to be an early indicator of poor outcome and a potential entry criterion for future studies with therapeutic intervention aiming at MIF neutralization.
Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis
Intensive Care Medicine, 2001
Objective: To investigate the role of macrophage migration inhibitory factor (MIF) as a marker of severity of systemic inflammation in patients with severe sepsis and critically ill postsurgical patients. Design: Prospective observational study in consecutive patients with severe sepsis, critically ill nonseptic postsurgical patients, and healthy blood donors. Setting: A surgical intensive care unit of a university hospital. Patients and
Scientific Reports, 2023
Macrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF are different between males and females. We conducted a single-center prospective, observational study with repeated measurements of MIF in serum and urine on days 0, 2, and 4 from admission to the intensive care unit (ICU) in 50 adult septic patients. We found that in patients who died within 90 days, there was an increase in serum MIF level from day 0 to 4, whereas in the survivors there was rather a decrease (p = 0.018). The kinetics were sexdependent as the same difference in the pattern was present in males (p = 0.014), but not in females (p = 0.418). We also found that urine MIF was markedly lower in patients who died than in survivors of sepsis (p < 0.050). Urine MIF levels did not show temporal changes: there was no meaningful difference between day 0 and 4. These results suggest that kinetics of serum MIF during the initial days from ICU admission can predict death, especially in male patients. Additionally, lower urine MIF levels can also indicate death without showing meaningful temporal kinetics.
Journal of the American College of Surgeons, 2018
Background: Acute kidney injury (AKI) refers to a broad spectrum of kidney damage and is attributed a high morbidity and mortality rate at all degrees of severity. Obesity increases the risk for developing AKI. However, some studies have shown that obesity at onset of AKI is paradoxically associated with greater survival. The aim of this review is to explore the relationship between body mass index and survival in patients with AKI. Methods: An electronic search will be conducted using MEDLINE, EMBASE, CINAHL and CENTRAL using predefined search strategies. The cited and citing references of selected key studies will also be searched for relevant articles. Risk of bias will be assessed using a modified Quality in Prognosis Studies (QUIPS) tool. The primary outcome will be an exploration of the association between BMI and mortality in patients presenting with AKI. Two authors will independently select, data extract, and risk of bias assess articles. Any discrepancies will be resolved by consensus or by consulting a third author. A narrative synthesis of the findings from the included studies will be presented. Meta-analyses will be conducted where the data is available from clinically and methodologically similar studies and in the same format. Heterogeneity in such analyses, beyond that expected by chance, will be quantified using the I 2 statistic. Subgroup analyses will be performed to determine the influence of gender, AKI duration, underlying aetiology, and intervening treatments, on pooled results. Discussion: Body mass index may be an important modifiable risk factor for mortality in patients presenting with AKI. The proposed systematic review will help to elucidate the association between all categories of BMI and survival in this patient group. Systematic review registration: PROSPERO CRD42017071124.
Clinical Infectious Diseases, 2007
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. Numerous adjunctive therapies for patients with severe sepsis and septic shock have been tested in clinical trials. Until recently, most antisepsis therapies yielded disappointing results. However, the use of drotrecogin alfa
This study aimed to evaluate the association of plasma MIF level and –173 G/C single nucleotide polymorphism of the MIF gene with the occurrence, severity and mortality of sepsis patients. A study was conducted in adult surgical intensive care units of Zagazig University Hospitals, Egypt on 25 patients with sepsis, 27 with severe sepsis and 28 controls. Gram-negative bacilli were the most common isolates in both severe sepsis (63.0%) and sepsis (56.0%) patients. A highly statistically significant difference was found in MIF levels between sepsis cases and controls and a statistically significant difference as regards MIF level in different genotypes of the studied groups. MIF level was significantly associated with mortality in sepsis cases. High MIF levels and MIF –173G/C gene polymorphism are powerful predictors of the severity of sepsis and its outcome. Pertinence fonctionnelle et pronostique du polymorphisme du gène – 173 G/C du facteur d'inhibition de la migration des macrophages chez des patients atteints de septicémie admis dans des unités de soins intensifs en Égypte RÉSUMÉ La présente étude visait à évaluer l'association entre le taux facteurs d'initiative de lamigration des macrophages (MIF) plasmatique et le polymorphisme du nucléotide simple – 173 G/C du gène MIF et l'occurrence, la sévérité ainsi que le taux de mortalité chez les patientsprésentant une septicémie. Une étude a été menée dans des unités de soins intensifs en chirurgie pour adultes de l'hôpital universitaire de Zagazig, (Égypte) auprès de 25 patients atteints de septicémie, de 27 patients atteints d'une septicémie sévère et de 28 témoins. Des bacilles à Gram négatif étaient les isolats les plus fréquents dans les cas de septicémie sévère (63,0 %) et de septicémie (56,0 %). Une différence statistiquement très importante a été observée entre les taux du facteur d'inhibition de la migration des macrophages des cas de septicémie et des témoins tandis qu'une différence statistiquement significative a été notée entre le taux MIF des différents génotypes des groupes étudiés. Le taux du facteur d'inhibition de la migration des macrophages était nettement associé à la mortalité dans les cas de septicémie. De forts taux MIF et le polymorphisme du gène – 173G/C du MIF sont de puissants facteurs prédictifs de la sévérité de la septicémie et de son issue.
Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations
Translational Research, 2007
Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine central to the response to endotoxemia, is a putative biomarker in acute lung injury (ALI). To explore MIF as a molecular target and candidate gene in ALI, we examined MIF gene and protein expression in murine and canine models of ALI (high tidal volume mechanical ventilation, endotoxin exposure) and in patients with either sepsis or sepsis-induced ALI. MIF gene expression and protein levels were significantly increased in each ALI model, with serum MIF levels significantly higher in patients with either sepsis or ALI compared to healthy controls (African-and European-descent). We next studied the association of 8 MIF gene polymorphisms (SNPs) (within a 9.7 kb interval on chromosome 22q11.23) with the development of sepsis and ALI in European-and African-descent populations. Genotyping in 506 DNA samples (sepsis patients, sepsis-associated ALI patients, and healthy controls) revealed haplotypes located in the 3′ end of the MIF gene, but not individual SNPs, associated with sepsis and ALI in both populations. These data, generated via functional genomic and genetic approaches, suggest that MIF is a relevant molecular target in ALI.