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: 6937668
• 负责人: Tasnee Chonmaitree
• 金额: $ 50万
• 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/6937668
• 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）：最常见的小儿疾病中耳炎（OM）被认为是多因素，具有复杂的遗传，环境和感染性病因。急性中耳炎（AOM）通常是儿童病毒上呼吸道感染（URI）的细菌并发症。证据表明，不同类型的病毒诱导AOM的能力有所不同。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的发病机理和恢复中的复杂相互作用，并确定可能的策略，以进行更有效的预防和/或治疗。拟议的5年研究将研究“宿主”和“微生物”在病毒诱导的AOM发展中的关系。我们将探索特定呼吸道病毒的致病性，以及促炎细胞因子（TNFCX，-IL-1B，IL-6）及其基因调节在病毒诱导的AOM机制中的作用。在AIM 1中，我们将研究病毒诱导的体内和体外AOM的差异细胞因子表达。我们将前瞻性地跟随210名婴儿和儿童，有和没有急性相细胞因子基因的多态性（TNFCX（-308，IB-+3953和IL-6等位基因）一年。在每个病毒性URI事件后3周内3周。作为并发症的风险，将评估与细胞因子基因型的关联，将在体外实验中研究特定病毒的细胞因子产生。基因和对OM的敏感性，使用了有或没有复发性OM病史的200名儿童的外周血。研究结果应改善人群中复发性OM的风险识别，这可能促进高风险群体的特定预防和治疗方法。这项研究还将为未来的创新方法设计，以防止或减少AOM的发病率，例如使用特定针对的病毒疫苗，抗病毒药物和免疫调节剂的疗法。