National Institutes of Health, International Center for Excellence in Research, Chennai, India.
PLoS Pathog. 2012;8(6):e1002749. doi: 10.1371/journal.ppat.1002749. Epub 2012 Jun 7.
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag-) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag- compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.
淋巴丝虫病可导致部分感染患者出现淋巴水肿、鞘膜积液和象皮病等严重病理变化。宿主炎症反应失调导致全身免疫激活，被认为在丝虫病发病机制中起核心作用。我们测量了慢性丝虫病病理患者（CP Ag+）或无活动性感染（CP Ag-）、临床无症状感染（INF）以及无感染（地方性正常[EN]）患者的血浆中微生物易位标志物、急性期蛋白和炎症细胞因子的水平。将两个活动性感染组（CP Ag+与 INF 相比）与无活动性感染组（CP Ag-与 EN 相比）进行比较，初步确定发病机制的标志物。然后，我们使用线性模型对数转换标志物的反应，在所有四个组之间测试组间效应。我们的数据表明，循环中微生物易位产物（脂多糖和脂多糖结合蛋白）、急性期蛋白（触珠蛋白和血清淀粉样蛋白 A）和炎症细胞因子（IL-1β、IL-12 和 TNF-α）的水平与淋巴丝虫感染的疾病发病机制有关，这表明循环微生物产物和急性期蛋白起着重要作用。
