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

Anne T. Kloek, Mercedes Valls Seron, Ben Schmand, Michael W. T. Tanck, Arie van der Ende, Matthijs C. Brouwer, Diederik van de Beek*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Article number4
JournalActa neuropathologica communications
Issue number1
Publication statusPublished - 1 Dec 2021

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