Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring
Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring
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DOI：
10.1176/appi.ajp.161.5.889
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发表时间：
2004-05-01
影响因子：
17.7
通讯作者：
Susser, ES
中科院分区：
文献类型：
--
作者：
Brown, AS;Hooton, J;Susser, ES
目的：许多研究表明，产前感染与精神分裂症的病因有关。细胞因子是一类可溶性多肽，在对感染的免疫反应和其他炎症过程中起着至关重要的作用。本研究的目的是确定晚发精神分裂症谱系障碍的母亲孕中期4种细胞因子--白介素8(IL-8)、白介素1β(IL-1β)、白介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平是否高于匹配的对照受试者。例(N=59)是被诊断为精神分裂症谱系障碍(主要是精神分裂症和分裂情感障碍)的受试者，他们有可用的第二次修剪酯类母体血清样本。对照受试者(N=105)是出生队列中的成员，未被诊断为精神分裂症谱系障碍或严重情感障碍，并在出生日期、性别、队列中的时间长短和母亲血清的可获得性方面与精神分裂症受试者匹配。采用双抗体夹心酶联免疫吸附试验检测孕中期血清IL-8、IL-1β、IL-6、TNF-α水平。结果：精神分裂症谱系障碍母亲孕中期IL-8水平显著高于对照组。在精神分裂症患者和对照组之间，母亲的IL-1β、IL-6或TNF-α水平没有差异。结论：使用前瞻性收集的大量和特征良好的出生队列中的产前血清，作者证明了母亲在中期妊娠期间的IL-8水平与子代精神分裂症谱系障碍的风险之间存在显著的相关性。这些发现进一步支持了宫内感染或炎症在精神分裂症病因中的实质性作用。此外，这些结果可能对阐明胎儿发育障碍增加这种疾病风险的机制具有重要意义。
Objective: Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 (IL-8), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects.Method: The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959-1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizo-affective disorder) who had available second-trim ester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder, and were matched to subjects with schizophrenia for date of birth, gender, length of time in the cohort, and availability of maternal sera. Maternal second-trimester serum levels of IL-8, IL-1beta, IL-6, and TNF-alpha were determined by sandwich enzyme-linked immunosorbent assay.Results: The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects. There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta, IL-6, or TNF-alpha.Conclusions: Using prospectively collected prenatal sera in a large and well-characterized birth cohort, the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring. These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia. Moreover, these results may have important implications for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder.