Nitric oxide in Tanzanian children with malaria: Inverse relationship between malaria severity and nitric oxide production nitric oxide synthase type 2 expression
Nitric oxide in Tanzanian children with malaria: Inverse relationship between malaria severity and nitric oxide production nitric oxide synthase type 2 expression
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DOI：
10.1084/jem.184.2.557
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发表时间：
1996-08-01
影响因子：
15.3
通讯作者：
Granger, DL
中科院分区：
文献类型：
--
作者：
Anstey, NM;Weinberg, JB;Granger, DL
一氧化氮（NO）相关的活性已被证明是保护对恶性疟原虫在体外。然而，据推测，过量的NO产生有助于脑型疟疾的发病机制。本研究的目的是比较191名坦桑尼亚疟疾患儿和非疟疾患儿的NO生成标志物[尿和血浆硝酸盐+硝酸盐（NOx）]、白细胞诱导型一氧化氮合酶2型（NOS 2）、血浆TNF-α和IL-10水平与疾病严重程度的关系。尿氮氧化物排泄和血浆氮氧化物水平（校正肾损害）与疾病严重程度呈负相关，亚临床感染水平最高，致命性脑型疟疾最低。结果不能用各组之间膳食硝酸盐摄入量的差异来解释。IL-10是一种已知抑制NO合成的细胞因子，其血浆水平随疾病严重程度而增加。白细胞NOS 2抗原检测在所有对照儿童测试和生病的所有那些亚临床感染，但在所有检测，但一个主题与脑型疟疾。脑型疟疾中NO合成的这种抑制可能有助于发病机制。相反，健康对照组和无症状感染者的高空腹NOx水平和白细胞NOS 2表明NO合成增加可能预防临床疾病。NO在非洲疟疾儿童中似乎具有保护作用，而不是病理作用。
Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrate (NOx)], leukocytc-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NOx excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Result could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and ill all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.