scholarly journals Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

2016 ◽  
Vol 113 (13) ◽  
pp. 3597-3602 ◽  
Author(s):  
Athina Savva ◽  
Matthijs C. Brouwer ◽  
Thierry Roger ◽  
Mercedes Valls Serón ◽  
Didier Le Roy ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Pneumococcal Meningitis ◽  
Inhibitory Factor ◽  
Morbidity And Mortality ◽  
High Expression ◽  
Macrophage Migration ◽  
Systemic Complications ◽  
Functional Polymorphisms

Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (−794 CATT5–8; rs5844572) and a single-nucleotide polymorphism (−173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and −173 C high-expression MIF alleles were associated with unfavorable outcome (P = 0.005 and 0.003) and death (P = 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P = 0.02] and carriage of the CATT7 allele (OR 5.12, P = 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P = 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.

scholarly journals Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Anne T. Kloek ◽  
Mercedes Valls Seron ◽  
Ben Schmand ◽  
Michael W. T. Tanck ◽  
Arie van der Ende ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Bacterial Meningitis ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Pneumococcal Meningitis ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Inhibitory Factor ◽  
Macrophage Migration

Abstract Background Patients with pneumococcal meningitis are at risk for death and neurological sequelae including cognitive impairment. Functional genetic polymorphisms of macrophage migration inhibitory factor (MIF) alleles have shown to predict mortality of pneumococcal meningitis. Methods We investigated whether MIF concentrations during the acute phase of disease were predictive for death in a nationwide prospective cohort study. Subsequently, we studied whether individual ex vivo MIF response years after meningitis was associated with the development of cognitive impairment. Results We found that in the acute illness of pneumococcal meningitis, higher plasma MIF concentrations were predictive for mortality (p = 0.009). Cognitive impairment, examined 1–5 years after meningitis, was present in 11 of 79 patients after pneumococcal meningitis (14%), as compared to 1 of 63 (2%) in controls, and was consistently associated with individual variability in MIF production by peripheral blood mononuclear cells after ex vivo stimulation with various infectious stimuli. Conclusions Our study confirms the role of MIF in poor disease outcome of pneumococcal meningitis. Inter-individual differences in MIF production were associated with long-term cognitive impairment years after pneumococcal meningitis. The present study provides evidence that MIF mediates long-term cognitive impairment in bacterial meningitis survivors and suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.

scholarly journals Macrophage migration inhibitory factor in Nodding syndrome

2021 ◽  
Vol 15 (10) ◽  
pp. e0009821
Author(s):  
Gil Benedek ◽  
Mahmoud Abed El Latif ◽  
Keren Miller ◽  
Mila Rivkin ◽  
Ally Ahmed Ramadhan Lasu ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Plasma Levels ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
High Expression ◽  
Macrophage Migration ◽  
Healthy Controls ◽  
Nodding Syndrome ◽  
Functional Polymorphisms ◽  
Autoimmune Epilepsy

Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)–a parasitic worm transmitted to human by blackflies. NS seems to be an ’Autoimmune Epilepsy’ in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a −794 CATT5–8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF -173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS.Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expression MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy.

scholarly journals Macrophage migration inhibitory factor: molecular, cellular and genetic aspects of a key neuroendocrine molecule

2004 ◽  
Vol 182 (1) ◽  
pp. 1-9 ◽  
Author(s):  
RP Donn ◽  
DW Ray
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inflammatory Diseases ◽  
Inhibitory Factor ◽  
Target Cells ◽  
Macrophage Migration ◽  
Signalling Molecules ◽  
Functional Polymorphisms ◽  
Low Concentrations

The immunological and neuroendocrine properties of macrophage migration inhibitory factor (MIF) are diverse. In this article we review the known cellular, molecular and genetic properties of MIF that place it as a key regulatory cytokine, acting within both the innate and adaptive immune responses.The unexpected and paradoxical induction of MIF secretion by low concentrations of glucocorticoids is explored. The role of MIF as a locally acting modulator of glucocorticoid sensitivity within foci of inflammation is also discussed. MIF has no homology with any other pro-inflammatory cytokine and until recently lacked a recognised transmembrane receptor. MIF has also been shown to be directly taken up into target cells and to interact with intracellular signalling molecules, including the Jun activation domain-binding protein Jab-1.Comprehensive analysis of the MIF gene has identified important functional polymorphisms and a series of genetic studies has revealed both association and linkage of MIF with inflammatory diseases. Altered MIF regulation may therefore be pivotal to acquiring chronic inflammation following an innate immune response.

High Expression of Macrophage Migration Inhibitory Factor in the Murine Lacrimal Gland

Cornea ◽  
2010 ◽  
Vol 29 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Choul Yong Park ◽  
Young Joo Shin ◽  
Kaevalin Lekhanont ◽  
Cheng Zhang ◽  
Woo-Seok Lee ◽  
...  
Keyword(s):  
Lacrimal Gland ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
High Expression ◽  
Macrophage Migration

HIGH EXPRESSION OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN THE SYNOVIAL TISSUES OF RHEUMATOID JOINTS

Cytokine ◽  
1999 ◽  
Vol 11 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Shin Onodera ◽  
Hiroshi Tanji ◽  
Kouji Suzuki ◽  
Kiyoshi Kaneda ◽  
Yuka Mizue ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
High Expression ◽  
Macrophage Migration ◽  
Synovial Tissues
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