Evidence that interferon-γ plays a protective role during cerebral malaria
Evidence that interferon-γ plays a protective role during cerebral malaria
复制标题
DOI：
10.1086/432484
复制
发表时间：
2005-09-01
影响因子：
6.4
通讯作者：
Marquet, S
中科院分区：
文献类型：
--
作者：
Cabantous, S;Poudiougou, B;Marquet, S
背景脑型疟疾（CM）的致病机制尚不清楚，但被认为涉及脑微循环中寄生虫隔离增强的精氨酸介导的炎症。干扰素-γ（IFN-γ）在增强炎症和减少寄生虫血症中的作用尚不清楚。采用酶联免疫吸附试验测定了96名CM儿童和40名来自Gabriel Toure医院（巴马科，马里）的无并发症疟疾（UM）儿童的血浆IFN-γ浓度。我们通过非参数分析研究了IFN-γ浓度与疾病之间的关系。IFNG的多态性的特点是限制性内切酶分析或大小测定电泳。对240个家系进行了多态性与CM的关联分析。在疟疾发作期间，CM儿童的IFN-g浓度低于UM儿童（P = .007）。IFNG-183 T（P = 0.009）和IFNG-183 G/T（P = 0.013）在CM儿童中的频率低于预期。IFNG（CA）（14）/（CA）（14）（P = 0.073）和CM之间也观察到相关趋势。IFNG-183 G/T和IFNG（CA）（14）/（CA）（14）基因型在UM患儿中的频率高于CM患儿（比值比分别为0.30和0.34）。CM儿童血浆IFN-γ浓度低，CM风险降低与（1）IFNG-183 T等位基因（增加基因转录）和（2）IFNG-183 G/ T基因型之间的相关性与IFN-γ预防CM的概念一致。
Background. The pathogenic mechanisms of cerebral malaria ( CM) are unclear but are thought to involve cytokine-mediated inflammation enhanced by parasite sequestration in the brain microcirculation. The role that interferon (IFN)-gamma could play that would enhance inflammation but also reduce parasitemia is unclear.Methods. Plasma IFN-gamma concentrations were measured by enzyme-linked immunosorbent assay in 96 children with CM and 40 children with uncomplicated malaria (UM) who had been recruited from Gabriel Toure Hospital (Bamako, Mali). We investigated the relationship between IFN-gamma concentrations and disease by nonparametric analysis. Polymorphisms in IFNG were characterized by restriction enzyme analysis or size-determination electrophoresis. Associations between polymorphisms and CM were evaluated by the family-based association test on 240 families.Results. During episodes of malaria, IFN-g concentrations were lower in children with CM than in children with UM (P = .007). IFNG-183T (P = .009) and IFNG-183G/T (P = .013) were found to be less frequent than expected in children with CM. A trend toward association was also observed between IFNG(CA)(14)/(CA)(14) (P = .073) and CM. The IFNG-183G/T and IFNG(CA)(14)/(CA)(14) genotypes were more frequent in children with UM than in children with CM (odds ratio, 0.30 and 0.34, respectively).Conclusions. The low plasma IFN-gamma concentrations in children with CM and the associations between a reduced risk of CM and (1) the IFNG-183T allele (which increases gene transcription) and (2) the IFNG-183G/ T genotype are consistent with the concept that IFN-gamma protects against CM.