TY - JOUR
T1 - Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis
AU - Kloek, Anne T.
AU - Seron, Mercedes Valls
AU - Schmand, Ben
AU - Tanck, Michael W. T.
AU - van der Ende, Arie
AU - Brouwer, Matthijs C.
AU - van de Beek, Diederik
N1 - Funding Information: This work was supported by grants from the European Research Council (ERC Starting Grant [proposal/contract 281156]), Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici Grant [Proposal/Contract 91819627]), both to D. van de Beek. The Netherlands Reference Laboratory for Bacterial Meningitis is supported by the National Institute of Public Health and the Environmental Protection, Bilthoven. The funders had no role in the design of the study, collection, analysis, and interpretation of data or in writing the manuscript. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Bacterial meningitis
KW - Cognitive impairment
KW - Macrophage migration inhibitory factor
KW - Pneumococcal meningitis
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85098770532&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33407905
UR - http://www.scopus.com/inward/record.url?scp=85098770532&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s40478-020-01100-7
DO - https://doi.org/10.1186/s40478-020-01100-7
M3 - Article
C2 - 33407905
SN - 2051-5960
VL - 9
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 4
ER -