EFFECT OF INFLUENZA VACCINATION ON CYTOCHROME P450

流感疫苗对细胞色素 P450 的影响

• 批准号: 6265758
• 负责人: Mary S. Hayney
• 金额: $ 3.35万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265758
• 关键词: clinical research; cytochrome P450; human subject; immunity; influenza vaccines; interleukin 6; liver metabolism

Influenza vaccination has an effect on the hepatic metabolism of many drugs. This study examines the immune mechanism behind the influence of influenza immunization on cytochrome P450 CYP3A4. Influenza unionization results in interleukin-6 (IL-6) production. IL-6 is a pro-inflammatory cytokine, which affects the liver by inducing acute phase reaction protein synthesis. In addition, IL-6 decreases the expression of CYP3A4 by cultured hepatocytes. Carbamazepine (a CYP3A4 substrate) levels in neurosurgery patients are associated with IL-6 levels. Our primary hypothesis is that the IL-6 production following influenza immunization is associated with changes in CYP3A4 activity. To substantiate this hypothesis, we will immunize fifteen subjects after measuring baseline IL-6 levels, influenza antibody levels, and CYP3A4 activity. Subjects will return for IL-6 levels and CYP3A4 activity determinations on Day 7 and for influenza antibody levels on Day 28. IL-6 and influenza antibody levels will be measured by ELISA. Erythromycin breath test (ERMBT) will be used to measure CYP3A4 activity. Data analyses include correlation of IL-6 levels with ERMBT changes. Secondarily, we will also compare the change in IL-6 levels and ERMBT before and after immunization and correlate with influenza vaccine antibody response. The proposed work represents a mechanistic approach to the study of influence of cytokine production elicited by immunization on hepatic drug metabolism. The clinical implications of this work include improved management of patients at the time of influenza immunization. The utility of this work extends beyond the clinic by demonstrating the utility of immunization as a probe to further the understanding of the immune system and its interaction with other physiological systems.

流感疫苗接种对许多药物的肝脏代谢有影响。本研究旨在探讨流感免疫对细胞色素P450 CYP 3A 4影响背后的免疫机制。 流感联合导致白细胞介素-6（IL-6）的产生。 IL-6是一种促炎细胞因子，其通过诱导急性期反应蛋白质合成来影响肝脏。 此外，IL-6降低了培养肝细胞的CYP 3A 4表达。卡马西平（CYP 3A 4底物）在神经外科患者中的水平与IL-6水平相关。 我们的主要假设是流感免疫后IL-6的产生与CYP 3A 4活性的变化有关。 为了证实这一假设，我们将在测量基线IL-6水平、流感抗体水平和CYP 3A 4活性后对15名受试者进行免疫接种。 受试者将在第7天返回进行IL-6水平和CYP 3A 4活性测定，并在第28天返回进行流感抗体水平测定。 将通过ELISA测量IL-6和流感抗体水平。 将使用红霉素呼气试验（ERMBT）测量CYP 3A 4活性。 数据分析包括IL-6水平与ERMBT变化的相关性。 其次，我们还将比较免疫前后IL-6水平和ERMBT的变化，并与流感疫苗抗体应答相关。 建议的工作代表了一种机制的方法来研究免疫引起的细胞因子的产生对肝脏药物代谢的影响。 这项工作的临床意义包括在流感免疫接种时改善对患者的管理。 这项工作的效用扩展到临床以外，通过展示免疫作为探针的效用，以进一步了解免疫系统及其与其他生理系统的相互作用。