Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Acta Neuropathol Commun. 2021 Jan 6;9(1):4. doi: 10.1186/s40478-020-01100-7.
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.
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.
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.
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.
患有肺炎球菌性脑膜炎的患者有死亡和神经后遗症的风险，包括认知障碍。巨噬细胞移动抑制因子 (MIF) 等位基因的功能性遗传多态性已被证明可预测肺炎球菌性脑膜炎的死亡率。
我们在一项全国性前瞻性队列研究中调查了疾病急性期 MIF 浓度是否可预测死亡。随后，我们研究了脑膜炎后个体体外 MIF 反应是否与认知障碍的发展有关。
我们发现，在肺炎球菌性脑膜炎的急性疾病中，较高的血浆 MIF 浓度与死亡率相关（p = 0.009）。肺炎球菌性脑膜炎后 1-5 年检查到认知障碍的患者有 11 例（14%），而对照组有 1 例（2%），并且与个体对外周血单个核细胞的 MIF 产生的个体差异一致在体外用各种感染性刺激物刺激后。
我们的研究证实了 MIF 在肺炎球菌性脑膜炎不良疾病结局中的作用。MIF 产生的个体差异与肺炎球菌性脑膜炎后多年的长期认知障碍有关。本研究提供了证据表明 MIF 介导细菌性脑膜炎幸存者的长期认知障碍，并表明 MIF 作为免疫调节辅助治疗的潜在靶点。
