EFFECT OF INFLUENZA VACCINATION ON CYTOCHROME P450

流感疫苗接种对许多药物的肝脏代谢都有影响。本研究旨在探讨流感免疫对细胞色素P450细胞色素P3A4影响的免疫机制。流感的结合导致白介素6(IL-6)的产生。IL-6是一种促炎细胞因子，通过诱导急性时相反应蛋白合成来影响肝脏。此外，IL-6还可降低培养的肝细胞中细胞色素P3A4的表达。神经外科患者的卡马西平水平(细胞色素P3A4底物)与IL-6水平相关。我们的主要假设是流感免疫后IL-6的产生与细胞色素P3A4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CYP3A4活性后对15名受试者进行免疫。受试者将在第7天回来进行IL-6水平和CYP3A4活性测定，并在第28天进行流感抗体水平测定。IL-6和流感抗体水平将通过酶联免疫吸附试验进行检测。采用红霉素呼气试验(ERMBT)测定细胞色素P3A4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，以及与流感疫苗抗体应答的相关性。这项拟议的工作代表了一种研究免疫诱导的细胞因子产生对肝脏药物代谢影响的机械方法。这项工作的临床意义包括在接种流感疫苗时改善对患者的管理。这项工作的用途超越了临床，展示了免疫作为探针的用途，以进一步了解免疫系统及其与其他生理系统的相互作用。

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.