Andersen Andreas, Jensen Kristoffer J, Erikstrup Christian, Ravn Henrik, Fisker Ane B, Lisse Ida M, Sartono Erliyani, Aaby Peter, Yazdanbakhsh Maria, Benn Christine S
Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institute, Copenhagen, Denmark; Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau.
Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
PLoS One. 2014 Apr 8;9(4):e93562. doi: 10.1371/journal.pone.0093562. eCollection 2014.
The mechanisms behind heterologous immunity and non-specific effects of vaccines on mortality are not well understood. We examined associations between cytokine responses and subsequent mortality in low-birth-weight infants in Guinea-Bissau.
A low-birth-weight trial randomized children to Bacille Calmette-Guérin (BCG) at birth or later according to local policy. Blood samples were obtained from a sub-group at age 6 weeks. Interleukin (IL)-5, IL-10, IL-13, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured in whole-blood cell cultures stimulated with lipopolysaccharide (LPS), phytohaemagglutinin (PHA), or purified protein derivative (PPD). The outcome was mortality between bleeding and 1 year of age. Non-linear associations between cytokine responses and mortality were examined.
Cytokine measurements were available from 390 children. The mortality rate (MR) was high (6.8/100 person-years-observation (PYO)). Both low and high cytokine responses to LPS and PHA were associated with high mortality (MR up to 25/100 PYO in the lowest 10% and 9.2/100 PYO in the highest 10%). In BCG-vaccinated children, higher IFN-γ responses to PPD were associated with better survival (MR ratio = 0.43 (0.24-0.77)).
Data presented a rare opportunity to explore associations between cytokine responses and mortality. Both low and high cytokine responses were associated with high mortality; a balanced response to invading pathogens seems preferable.
疫苗的异源免疫及对死亡率的非特异性影响背后的机制尚未完全明确。我们研究了几内亚比绍低体重婴儿细胞因子反应与随后死亡率之间的关联。
一项低体重儿试验根据当地政策将儿童随机分为出生时或之后接种卡介苗（BCG）两组。在6周龄时从一个亚组采集血样。在脂多糖（LPS）、植物血凝素（PHA）或纯化蛋白衍生物（PPD）刺激的全血细胞培养物中测量白细胞介素（IL）-5、IL-10、IL-13、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α。观察结局为采血至1岁时的死亡率。研究了细胞因子反应与死亡率之间的非线性关联。
390名儿童有细胞因子测量数据。死亡率（MR）较高（6.8/100人年观察期（PYO））。对LPS和PHA的低细胞因子反应及高细胞因子反应均与高死亡率相关（最低10%的MR高达25/100 PYO，最高10%的为9.2/100 PYO）。在接种BCG的儿童中，对PPD的较高IFN-γ反应与更好的生存率相关（MR比值 = 0.43（0.24 - 0.77））。
数据提供了一个探索细胞因子反应与死亡率之间关联的难得机会。低细胞因子反应和高细胞因子反应均与高死亡率相关；对入侵病原体的平衡反应似乎更为可取。
