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Updated: Nov 22, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after
Anne T Kloek1, Mercedes Valls Seron1, Ben Schmand2,3
1Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
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.
Insights
Macrophage migration inhibitory factor (MIF) levels during acute pneumococcal meningitis predict mortality. Individual MIF production variability is linked to long-term cognitive impairment in survivors, suggesting MIF as a therapeutic target.
Area of Science:
- Immunology
- Neurology
- Infectious Diseases
Background:
- Pneumococcal meningitis poses risks of mortality and neurological deficits, including cognitive impairment.
- Genetic variations in macrophage migration inhibitory factor (MIF) alleles have been linked to pneumococcal meningitis mortality.
- The role of MIF in predicting disease outcomes and long-term sequelae requires further investigation.
Purpose of the Study:
- To determine if acute-phase MIF concentrations predict mortality in pneumococcal meningitis.
- To investigate the association between ex vivo MIF response and cognitive impairment development years after meningitis.
Main Methods:
- A nationwide prospective cohort study was conducted.
- Plasma MIF concentrations were measured during the acute phase of pneumococcal meningitis.
- Ex vivo MIF production by peripheral blood mononuclear cells was assessed years after meningitis.
Main Results:
- Elevated plasma MIF concentrations in the acute phase of pneumococcal meningitis predicted mortality (p=0.009).
- Cognitive impairment occurred in 14% of pneumococcal meningitis survivors (1-5 years post-infection) compared to 2% in controls.
- Individual differences in ex vivo MIF production after stimulation were consistently associated with cognitive impairment.
Conclusions:
- MIF plays a significant role in poor outcomes of pneumococcal meningitis.
- Inter-individual differences in MIF production are associated with long-term cognitive impairment in meningitis survivors.
- MIF may serve as a target for immune-modulating adjunctive therapy in bacterial meningitis.
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