Oyegue-Liabagui Sandrine Lydie, Bouopda-Tuedom Aline Gaëlle, Kouna Lady Charlène, Maghendji-Nzondo Sydney, Nzoughe Herman, Tchitoula-Makaya Nina, Pegha-Moukandja Irene, Lekana-Douki Jean-Bernard
Ecole Doctorale Régionale d'Afrique Centrale en Infectiologie Tropicale, Université des Sciences et Techniques de Masuku (USTM) Franceville B.P. 876 Franceville, Gabon.
Centre International de Recherches Médicales de Franceville (CIRMF) B.P. 769 Franceville, Gabon.
Am J Clin Exp Immunol. 2017 Feb 15;6(2):9-20. eCollection 2017.
Severe malaria anemia (SMA) is a major cause of mortality in pediatric wards. Variations in inflammatory mediator production play an essential role in disease outcomes. Indeed, several studies have shown the involvement of pro- and anti-inflammatory cytokines such as IFN-γ, IL-6, TNF-α and IL-10 in malaria immunopathology. In other hand the exact role of Th17 cytokines such as IL-17, IL-22 and IL-21 in malaria remains poorly documented. Here, we investigated IFN-γ, TNF-α, IL-6, IL-12, IL-10, IL-4, IL-13, IL-17, IL-22 and IL-21 circulating levels and their association with malaria anemia and parasitemia in Gabonese children. Levels of IFN-γ (500 ± 100.2 pg/ml), IL-6 (64 ± 14.2 pg/ml), IL-10 (505 ± 35 pg/ml), IL-13 (30.6 ± 5.6 pg/ml) were significantly higher ( < 0.03) in infected children than in uninfected controls (210 ± 20 pg/ml, 17.5 pg/ml, 50 ± 25.9, pg/ml, 17.48 pg/ml, respectively). IFN-γ levels were significantly lower ( = 0.04) in children with SMA (400 ± 200 pg/ml) than in those with uncomplicated malaria (900 ± 450 pg/ml) and higher in those with parasitemia ( = 0.019). Levels of IL-6 and IL-10 were significantly higher in children with malarial anemia ( < 0.001) and hyperparasitemia ( < 0.0001). A significant association between IL-10 levels and parasite density was observed ( < 0.00001). IL-22 levels were significantly higher ( = 0.01) in infected children (72.57 ± 7.5 pg/ml) than in the controls (54.96 ± 1.93 pg/ml). IL-21 levels (44.46 ± 17.27 pg/ml) decreased with the severity of anemia ( < 0.05), whereas IL-17 levels increased in children with SMA (12.25 ± 1.25 pg/ml) than in those with mild malaria anemia (MMA: 6.2 ± 5.25 pg/ml, = 0.002). Data suggest possible role of IFN-γ in the protection against SMA and parasite clearance. However, IL-6 and IL-10 could play a role in inflammatory response and pathophysiology of severe malaria anemia. Also, the role of IL-22 and IL-17 in malaria infection should be investigated.
严重疟疾贫血（SMA）是儿科病房死亡的主要原因。炎症介质产生的变化在疾病转归中起重要作用。事实上，多项研究表明促炎和抗炎细胞因子如干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）参与了疟疾免疫病理学过程。另一方面，白细胞介素-17（IL-17）、白细胞介素-22（IL-22）和白细胞介素-21（IL-21）等辅助性T细胞17（Th17）细胞因子在疟疾中的具体作用仍鲜有文献记载。在此，我们调查了加蓬儿童中IFN-γ、TNF-α、IL-6、IL-12、IL-10、IL-4、IL-13、IL-17、IL-22和IL-21的循环水平及其与疟疾贫血和寄生虫血症的关联。感染儿童的IFN-γ（500±100.2皮克/毫升）、IL-6（64±14.2皮克/毫升）、IL-10（505±35皮克/毫升）、IL-13（30.6±5.6皮克/毫升）水平显著高于未感染对照组（分别为210±20皮克/毫升、17.5皮克/毫升、50±2 .9皮克/毫升、17.48皮克/毫升）（P<0.03）。SMA患儿的IFN-γ水平（400±200皮克/毫升）显著低于非复杂性疟疾患儿（900±450皮克/毫升）（P = 0.04），而寄生虫血症患儿的IFN-γ水平较高（P = 0.019）。疟疾贫血患儿（P<0.001）和高寄生虫血症患儿（P<0.0001）的IL-6和IL-10水平显著更高。观察到IL-10水平与寄生虫密度之间存在显著关联（P<0.00001）。感染儿童的IL-22水平（72.57±7.5皮克/毫升）显著高于对照组（54.96±1.93皮克/毫升）（P = 0.01）。IL-21水平（44.46±17.27皮克/毫升）随贫血严重程度降低（P<0.05），而SMA患儿的IL-17水平（12.25±1.25皮克/毫升）高于轻度疟疾贫血患儿（MMA：6.2±5.25皮克/毫升，P = 0.002）。数据表明IFN-γ在预防SMA和清除寄生虫方面可能发挥作用。然而，IL-6和IL-10可能在严重疟疾贫血的炎症反应和病理生理学中起作用。此外，应研究IL-22和IL-17在疟疾感染中的作用。
