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。登革热感染在营养缺乏的人群中高度流行；然而，对于这些缺陷在从登革热发展为危及生命的登革热形式，包括登革出血热和登革休克综合征（DHF/DSS）中可能发挥的作用，人们知之甚少。从饮食中获得的脂肪酸在免疫和炎症调节中起着重要作用。来自鱼类的N-3多不饱和脂肪酸（PUFA）通过溶解蛋白（一种作用于中性粒细胞、巨噬细胞、树突状细胞和T细胞的代谢产物）的作用表现出强大的抗炎和消炎特性。N-3 PUFA还通过改变核转录因子b的活性来减少单核细胞促炎细胞因子的产生

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.