Jason J, Archibald L K, Nwanyanwu O C, Bell M, Buchanan I, Larned J, Kazembe P N, Dobbie H, Parekh B, Byrd M G, Eick A, Han A, Jarvis W R
HIV Immunology and Diagnostics Branch, Centers for Disease Control and Prevention, U.S. Public Health Service, Atlanta, Georgia 30333, USA.
Clin Immunol. 2001 Aug;100(2):208-18. doi: 10.1006/clim.2001.5057.
The balance between pro- and antiinflammatory cytokines may be important in malaria presentation and outcome. Malaria tends to be more severe in children than in adults, presumably because partial immunity develops with age. However, the full nature of, and age-related differences in, anti-malarial immunity are unknown. We compared: (1) serum and cell-specific cytokines of patients with acute malaria to those of patients with other acute illnesses and to those of healthy adults and (2) the cytokine responses of parasitemic children and parasitemic adults. Flow cytometry was done on the peripheral blood mononuclear cells of 148 hospitalized children, 161 febrile hospitalized adults, and 20 healthy adults in Malawi, Africa, a malaria-endemic country. Serum cytokines were also assessed for 80 of these patients. Thirty-eight participants were parasitemic with Plasmodium falciparum. Serum interleukin (IL)-10 (an antiinflammatory, immunoregulatory, and type 2 cytokine) levels were higher in malaria patients than in other patients (medians 502 pg/mL vs 16 pg/mL, P = 0.002), and the percentages of various lymphocyte populations making IL-6 (a proinflammatory, type 2 cytokine regulating iron distribution) were lower in malaria patients than in other patients (e.g., for spontaneous production by children's CD8(+) T cells: medians 1.4% vs 33.1%, P = 0.004). For adult patients, the percentages of lymphocytes spontaneously making IL-4 (a type 2 cytokine) were significantly lower in those with malaria than in those without malaria (medians 0.9% vs 2.1%, P = 0.005). The percentages of monocytes spontaneously making IL-8 (a chemotactic, proinflammatory chemokine) were higher in parasitemic children than in parasitemic adults (medians 5.8% vs 1.7%, P = 0.003). A number of cellular proinflammatory, type 1 parameters were significantly higher in all children (with or without malaria) than in all adults; these included the percentages of various lymphocyte populations making IL-6, both IL-6 and interferon-gamma, or IL-8. These data support the importance of IL-10 in malaria parasitemia. Given the lack of an IL-4 (type 2) response, IL-10's primary role may be immunoregulatory rather than type 2 in nature. In this study, the immune response to malaria was more proinflammatory in children than in adults. This difference, if corroborated by other studies, could be related to malaria's greater severity in children.
促炎细胞因子和抗炎细胞因子之间的平衡可能在疟疾的表现和转归中起重要作用。疟疾在儿童中往往比在成人中更严重，推测是因为随着年龄增长会产生部分免疫力。然而，抗疟疾免疫的完整本质以及与年龄相关的差异尚不清楚。我们进行了以下比较：（1）急性疟疾患者的血清和细胞特异性细胞因子与其他急性疾病患者以及健康成年人的血清和细胞特异性细胞因子；（2）有疟原虫血症的儿童和有疟原虫血症的成年人的细胞因子反应。在非洲疟疾流行国家马拉维，对148名住院儿童、161名发热住院成人和20名健康成年人的外周血单个核细胞进行了流式细胞术检测。还对其中80名患者的血清细胞因子进行了评估。38名参与者感染了恶性疟原虫。疟疾患者血清白细胞介素（IL）-10（一种抗炎、免疫调节和2型细胞因子）水平高于其他患者（中位数分别为502 pg/mL和16 pg/mL，P = 0.002），并且产生IL-6（一种调节铁分布的促炎、2型细胞因子）的各种淋巴细胞群体的百分比在疟疾患者中低于其他患者（例如，儿童CD8(+)T细胞自发产生IL-6的情况：中位数分别为1.4%和33.1%，P = 0.004）。对于成年患者，有疟疾的患者中自发产生IL-4（一种2型细胞因子）的淋巴细胞百分比显著低于无疟疾的患者（中位数分别为0.9%和2.1%，P = 0.005）。有疟原虫血症的儿童中自发产生IL-8（一种趋化性促炎趋化因子）的单核细胞百分比高于有疟原虫血症的成年人（中位数分别为5.8%和1.7%，P = 0.003）。一些细胞促炎1型参数在所有儿童（无论有无疟疾）中均显著高于所有成年人；这些参数包括产生IL-6、IL-6和干扰素-γ或IL-8的各种淋巴细胞群体的百分比。这些数据支持IL-10在疟疾疟原虫血症中的重要性。鉴于缺乏IL-4（2型）反应，IL-10的主要作用可能本质上是免疫调节而非2型作用。在本研究中，儿童对疟疾的免疫反应比成年人更具促炎性。如果其他研究证实了这种差异，可能与疟疾在儿童中更严重有关。
