EFFECT OF INFLUENZA VACCINATION ON CYTOCHROME P450

流感疫苗对许多药物的肝脏代谢有影响。本研究探讨流感免疫对细胞色素P450 CYP3A4影响的免疫机制。流感合并导致白细胞介素-6 （IL-6）的产生。IL-6是一种促炎细胞因子，通过诱导急性期反应蛋白合成来影响肝脏。此外，IL-6可降低培养的肝细胞中CYP3A4的表达。卡马西平（一种CYP3A4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CYP3A4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名受试者进行免疫接种。受试者将在第7天返回检测IL-6水平和CYP3A4活性，并在第28天检测流感抗体水平。IL-6和流感抗体水平将通过ELISA检测。红霉素呼气试验（ERMBT）将用于测量CYP3A4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的变化及其与流感疫苗抗体反应的相关性。本研究为研究免疫引起的细胞因子产生对肝脏药物代谢的影响提供了一种机制方法。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。这项工作的效用超越了临床，通过展示免疫作为进一步了解免疫系统及其与其他生理系统相互作用的探针的效用。

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.