Biochemical and Behavioral Correlates of IFN Response

干扰素反应的生化和行为相关性

• 批准号: 6943426
• 负责人: JENNIFER M LOFTIS
• 金额: $ 5.04万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6943426
• 关键词: antidepressants; biochemistry; clinical research; cytokine; depression; hepatitis C virus; human subject; interferon alpha; neuropsychology; nitric oxide synthase; postdoctoral investigator; serotonin; tryptophan

DESCRIPTION (provided by applicant): Interferon-a (IFN) is the only approved medication for hepatitis C viral (HCV) infection. However, side effects associated with IFN therapy represent a major obstacle to adequate treatment for patients with HCV, often resulting in the discontinuation IFN therapy. It is hypothesized that common mechanisms contribute to IFN-induced depression and antiviral effects. Two of IFN's antiviral mechanisms, 1) activation of inducible nitric oxide synthase (iNOS) and 2) induction of indoleamine 2,3-dioxygenase, which depletes tryptophan, involve mechanisms also hypothesized to cause depression. To accomplish the objectives of this grant, three specific aims will be pursued: 1) determine how plasma nitrite, tryptophan, and serotonin levels relate to IFN therapeutic response and depressive symptoms; 2) identify the effects of iNOS inhibition and serotonergic antidepressants on the proliferative response of T cells to HCV-derived antigens; and 3) evaluate antidepressant treatment on IFN-induced biochemical and therapeutic effects. Results will contribute to knowledge of IFN mechanisms that are important in HCV and in understanding depressive symptoms accompanying medical conditions where cytokines are elevated.

描述（由申请人提供）： 干扰素-a（IFN）是唯一批准用于治疗丙型肝炎病毒（HCV）感染的药物。然而，与IFN治疗相关的副作用是HCV患者充分治疗的主要障碍，通常导致IFN治疗的中止。据推测，共同的机制有助于干扰素诱导的抑郁症和抗病毒作用。IFN的两种抗病毒机制，1）诱导型一氧化氮合酶（iNOS）的活化和2）吲哚胺2，3-双加氧酶的诱导，其消耗色氨酸，涉及也被假设为引起抑郁症的机制。为了实现这项资助的目标，将追求三个具体目标：1）确定血浆亚硝酸盐，色氨酸和5-羟色胺水平如何与干扰素治疗反应和抑郁症状相关; 2）确定iNOS抑制和抗抑郁药对T细胞对HCV衍生抗原的增殖反应的影响; 3）评估抗抑郁药治疗对干扰素诱导的生化和治疗效果。结果将有助于IFN机制的知识，是重要的HCV和了解抑郁症状伴随的医疗条件下，细胞因子升高。