Fatty Acids & Risk of Dengue Hemorrhagic Fever

描述（由申请人提供）：营养状况是感染风险和结果的有力预测因素。登革感染在营养缺乏的人群中是高度流行的;然而，关于这些缺乏在从登革热发展为威胁生命的登革热形式，包括登革出血热和登革休克综合征（DHF/DSS）的过程中所起的作用，人们知之甚少。从饮食中获得的脂肪酸作为免疫和炎症的调节剂发挥重要作用。来自鱼类的N-3多不饱和脂肪酸（PUFA）通过作用于中性粒细胞、巨噬细胞、树突细胞和T细胞的消退素（resolvins）、代谢产物的作用而表现出有效的抗炎和炎症消退特性。N-3 PUFA还通过改变核转录因子B的活性来减少单核细胞产生促炎细胞因子。一些n-6脂肪酸表现出 抗病毒活性。此外，PUFA掺入免疫细胞膜微结构域调节MHC表面表达和抗原呈递活性。这些机制中的一些可能参与DHF/DSS的病理生理学，但脂肪酸对登革热感染进展为严重表现的潜在作用尚不清楚。在这项研究中，我们研究了诊断为登革热（DF）的患者血清n-3和n-6脂肪酸浓度及其发展DHF/DSS的风险之间的关系。我们将在哥伦比亚布卡拉曼加市门诊健康中心诊断为DF的患者队列中进行前瞻性研究。将在急性发作随访期间发生DHF/DSS的124例患者和未进展为DHF/DSS的504例患者之间比较DF诊断时的血清脂肪酸谱。这项研究的结果将提供一个基础，以考虑在急性DF治疗期间补充这些廉价营养素的效果，以防止进展为严重形式的疾病。

DESCRIPTION (provided by applicant): The nutritional status is a strong predictor of the risk and outcome of infections. Dengue infection is highly endemic in populations that are subject to nutritional deficiencies; yet little is known regarding the role that those deficiencies could playon the progression from dengue fever to life-threatening forms of dengue, including dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). Fatty acids obtained from diet play a significant role as modulators of immunity and inflammation. N-3 polyunsaturated fatty acids (PUFA) from fish exhibit potent anti-inflammatory and inflammation-resolving properties through the actions of resolvins, metabolic products that act on neutrophils, macrophages, dendritic cells, and T cells. N-3 PUFA also decrease mononuclear cell production of pro-inflammatory cytokines by modifying the activity of nuclear transcription factor B. Some n-6 fatty acids exhibit antiviral activity. In addition, incorporation of PUFA into immune cell membrane microdomains modulates MHC surface expression and antigen presentation activity. Several of these mechanisms may be involved in the pathophysiology of DHF/DSS but the potential role of fatty acids on progression to severe manifestations of dengue infection is unknown. In this study we examine the associations of serum n-3 and n-6 fatty acid concentrations among patients diagnosed with dengue fever (DF) and their risk of developing DHF/DSS. We will conduct a prospective investigation in the context of a cohort of patients diagnosed with DF at ambulatory health centers of the city of Bucaramanga, Colombia. The serum fatty acids profile at the time of DF diagnosis will be compared between 124 patients who developed DHF/DSS during follow-up of the acute episode and 504 patients who did not progress to DHF/DSS. Results of this study will provide a basis to consider the effect of supplementation with these inexpensive nutrients during treatment of acute DF to prevent progression to severe forms of the disease.