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.
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