Pathogenesis of Virus-Induced Acute Otitis Media

病毒引起的急性中耳炎的发病机制

• 批准号: 6661983
• 负责人: Tasnee Chonmaitree
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-20 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661983
• 关键词: adult human (21+); bacteria infection mechanism; bacterial cytopathogenic effect; bacterial disease; child (0-11); clinical research; epidemiology; gene expression; genetic polymorphism; genetic susceptibility; genotype; host organism interaction; human subject; interleukin 1; interleukin 6; longitudinal human study; microorganism interaction; opportunistic infections; otitis media; pathologic process; patient oriented research; respiratory infections; secondary infection; tumor necrosis factor alpha; virus cytopathogenic effect; virus diseases

DESCRIPTION (provided by applicant): Otitis media (OM), the most common pediatric disease, is recognized to be multifactorial, with complex genetic, environmental and infectious etiologies. Acute otitis media (AOM) usually occurs as a bacterial complication of viral upper respiratory tract infection (URI) in children. Evidence suggests that different types of viruses vary in their ability to induce AOM. The long-term objectives of our research group are to elucidate the contribution of viruses, bacteria and their complex interactions in the pathogenesis of and recovery from AOM, and to identify possible strategies for more effective prevention and/or treatment. The proposed 5-year study will investigate the relationship between "host" and "microbe" in the development of virus-induced AOM. We will explore the pathogenicity of specific respiratory viruses, and the role of proinflammatory cytokines (TNFcx, -IL-1B, IL-6) and their gene regulation in the mechanisms of virus-induced AOM. In Aim 1, we will study differential cytokine expression in virus-induced AOM in vivo and in vitro. We will prospectively follow 210 infants and children, with and without polymorphisms of acute phase cytokine genes (TNFcx(-308, IB-+3953, and IL- 6 alleles) for one year. For 3 weeks after each viral URI episode, we will monitor for the occurrence of AOM. We will compare virus type and cytokine concentrations in respiratory secretions from children who do and who do not develop AOM as a complication. Risk for AOM development will be evaluated for association with cytokine genotypes. In the in vitro experiments, induction of cytokine production by specific viruses will be studied in peripheral blood mononuclear leukocytes from healthy adult volunteers with normal or polymorphic cytokine genes. Aim 2 will retrospectively evaluate the association between polymorphisms of proinflammatory cytokine genes and susceptibility to OM, using peripheral blood from 200 children with and without a history of recurrent OM. These studies will clarify the role of specific respiratory viruses, proinflammatory cytokines, and their gene regulation in the pathogenetic mechanisms of virus-induced AOM. Study results should improve risk identification for recurrent OM in the population, which may facilitate specific prophylactic and therapeutic approaches for the high risk groups. The study will also lay the ground work for the future design of innovative approaches to prevent or reduce morbidity of AOM, such as therapies using specifically targeted viral vaccines, antiviral drugs, and immunomodulators.

描述（由申请人提供）：中耳炎（OM）是最常见的儿科疾病，被认为是多因素影响的，具有复杂的遗传、环境和感染病因。急性中耳炎 (AOM) 通常是儿童病毒性上呼吸道感染 (URI) 的细菌并发症。有证据表明，不同类型的病毒诱导 AOM 的能力各不相同。我们研究小组的长期目标是阐明病毒、细菌及其复杂相互作用在 AOM 发病机制和恢复中的作用，并确定更有效的预防和/或治疗的可能策略。拟议的为期 5 年的研究将调查“宿主”和“微生物”在病毒诱导的 AOM 发展中的关系。我们将探讨特定呼吸道病毒的致病性，以及促炎细胞因子（TNFcx、IL-1B、IL-6）及其基因调控在病毒诱导的 AOM 机制中的作用。在目标 1 中，我们将在体内和体外研究病毒诱导的 AOM 中细胞因子表达的差异。我们将前瞻性地跟踪 210 名婴儿和儿童，为期一年，无论有或没有急性期细胞因子基因（TNFcx（-308、IB-+3953 和 IL-6 等位基因）多态性。每次病毒 URI 发作后 3 周，我们将我们将比较发生和未发生 AOM 的儿童呼吸道分泌物中的病毒类型和细胞因子浓度，并评估 AOM 发生的风险。在体外实验中，将在具有正常或多态性细胞因子基因的健康成年志愿者的外周血单核白细胞中研究特定病毒诱导细胞因子产生的情况，目的2将回顾性评估促炎性细胞因子基因多态性之间的关联。使用来自 200 名有或没有复发 OM 病史的儿童的外周血，研究了 OM 和对 OM 的易感性。这些研究将阐明特定呼吸道病毒、促炎细胞因子及其基因调控的作用。病毒诱导的 AOM 的发病机制。研究结果应改善人群中复发性 OM 的风险识别，这可能有助于针对高危人群采取特定的预防和治疗方法。该研究还将为未来设计预防或减少 AOM 发病率的创新方法奠定基础，例如使用专门针对病毒的疫苗、抗病毒药物和免疫调节剂进行治疗。