Social and psychological risk for infectious illness

描述（由申请人提供）：我们的主要目标是评估社会环境对上呼吸道疾病易感性的影响，并确定环境因素“深入皮肤”影响疾病表达的途径。我们假设社会环境影响行为，下丘脑-垂体-肾上腺皮质（HPA）和自主神经系统（ANS）反应，进而影响对病毒的细胞和体液免疫反应的调节。我们采用独特的前瞻性设计。我们首先评估了260名攻毒病毒抗体血清阴性的健康成人的社会环境特征和行为和生理系统状态，我们预测这些特征与宿主耐药性有关。随后，我们通过鼻内滴剂将每个受试者暴露于两种鼻病毒株中的一种，并在封闭环境中密切监测他们的感染和疾病证据。在回廊之前和回廊期间每天收集的疾病测量包括病毒脱落和滴度、鼻腔促炎、抗炎和抗病毒细胞因子的产生、鼻腔和一般症状、体温、鼻分泌物产生和鼻粘膜纤毛清除功能。利用这些数据，我们将确定社会环境是否通过改变基线细胞免疫状态（延迟型超敏反应）、Th-1/Th-2细胞因子平衡和产生促炎细胞因子的能力（来自有丝分裂原刺激的外周血单个核细胞）来影响疾病表达；是否影响机体对感染反应中细胞因子产生的调节；以及社会环境和免疫之间的关联是否由ANS（分离交感神经和副交感神经的贡献）和/或HPA系统介导。所有的分析都将控制人口因素，并将关注社会环境是否能预测临床疾病（确诊感染+临床诊断）。本研究的结果将确定一个人的社会环境影响其对上呼吸道病毒感染易感性的途径，并可能确定行为或药物干预的潜在目标，以恢复因其社会环境而处于最高风险的人的疾病抵抗力。

DESCRIPTION (provided by applicant): Our primary goals are to assess the influence of the social environment on susceptibility to upper respiratory illness and to identify the pathways through which environmental factors "get under the skin" to influence disease expression. We hypothesize that the social environment influences behavior, hypothalamic-pituitary-adrenocortical (HPA) and autonomic nervous system (ANS) responses which in turn influence the regulation of both cellular and humoral immune response to the virus. We use a unique prospective design. We first assess characteristics of the social environment and the status of behavioral and physiological systems we predict to link these characteristics to host resistance in 260 healthy adults who are seronegative for antibodies to the challenge virus. Subsequently, we expose each subject by intranasal drops to one of two strains of rhinovirus and monitor them closely for evidence of infection and illness in a cloistered environment. Measures of illness collected immediately before and daily during the cloister include virus shedding and titer, nasal pro-inflammatory, anti-inflammatory and anti-viral cytokine production, nasal and general symptoms, body temperature, nasal secretion production and nasal mucociliary clearance function. Using these data, we will determine if the social environment influences illness expression by altering baseline cellular immune status (delayed type hypersensitivity), Th-1/Th-2 cytokine balance, and the ability to produce pro-inflammatory cytokines (from mitogen stimulated peripheral blood mononuclear cells); whether it influences the regulation of cytokine production in response to the infection; and whether the association between the social environment and immunity are mediated by the ANS (separating sympathetic and parasympathetic contributions) and/or HPA systems. All analyses will control for demographic factors and will focus on whether the social environment predicts clinical illness (verified infection + clinical diagnosis). The results of this study will define the pathways by which one's social environment influences their susceptibility to upper respiratory virus infection and may identify potential targets for behavioral or pharmaceutical interventions to restore disease resistance in persons most at risk because of their social environments.