Centro de Investigação em Saúde da Manhiça, Manhiça, Mozambique.
BMC Immunol. 2012 Jan 26;13:5. doi: 10.1186/1471-2172-13-5.
Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months.
IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months.
Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility.
ClinicalTrials.gov: NCT00209795.
细胞因子和趋化因子是抗疟免疫的关键介质。我们评估了婴儿磺胺多辛-乙胺嘧啶间歇性预防治疗（IPTi-SP）是否会影响莫桑比克儿童获得这些细胞免疫应答。在 5、9、12 和 24 个月时，通过 Luminex 定量测定血浆中的多种细胞因子和趋化因子，通过细胞内细胞因子染色和流式细胞术测定全血中的抗原特异性细胞因子产生。
IPTi-SP 对 CD3+细胞产生 IFN-γ、IL-4 或 IL-10 的比例没有显著影响。总体而言，治疗组之间的血浆细胞因子或趋化因子浓度没有差异。Th1 和促炎反应高于 Th2 和抗炎反应，并且 IFN-γ：IL-4 比值对于安慰剂组高于 SP 组。细胞因子和趋化因子的水平根据年龄而变化，从 5 个月下降到 9 个月。IL-10、IL-12 和 IL-13 的血浆浓度与当前感染或先前疟疾发作有关。较高的 IFN-γ和 IL-10 产生的 CD3+细胞频率以及较高的 IL-10、IFN-γ、MCP-1 和 IL-13 血浆浓度分别与不同时间点的疟疾发病率增加相关。当所有标志物一起分析时，只有 12 个月时更高的 IL-17 与 24 个月时的疟疾发病率降低相关。
我们的工作证实，IPTi-SP 不会对儿童早期细胞免疫反应的发展产生负面影响。本研究还提供了新的见解，即这些细胞因子反应是如何随着年龄和暴露于恶性疟原虫而获得的，以及它们与疟疾易感性的关系。
ClinicalTrials.gov：NCT00209795。
