The Immunomodulatory Effects of Phlebotomy
试验速览
- 阶段
- 不适用
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- ex vivo TNF-afpha production of whole blood in reponse to incubation with E. Coli LPS
研究概览
简要总结
Although phlebotomy is routinely performed in blood donors, and seemingly does not have significant health risks, it is highly relevant to know what the effect of phlebotomy is on immunity. Alterations in immunity due to phlebotomy could have beneficial effects, like the suppression of the low grade inflammatory process that contributes to atherosclerosis, but in theory could also contribute to a suppressed innate immune response that could increase the risk of infection. This is not only relevant for blood donors, but also for patients suffering from blood loss and for daily clinical practice in which blood is routinely drawn of patients for laboratory determinations.
详细描述
The loss of blood by haemorrhage or routine phlebotomy as performed during blood donation by healthy volunteers, has large effects on systemic iron homeostasis. The relative shortage of erythrocytes after blood loss is compensated for by increasing the production of new red cells by the bone marrow. As iron is needed for effective haemoglobin synthesis, the transport of iron to the bone marrow needs to be increased. This is accomplished by the suppression of hepcidin production in the liver. Hepcidin is the central regulator of iron homeostasis. It can regulate serum iron levels effectively by downregulating iron channel ferroportin on iron exporting cells. Hepcidin production is increased in response to inflammation en high systemic iron content, and is suppressed by increased erythrocyte production, hypoxia, anemia, and low systemic iron content. Therefore, blood loss leads to hepcidin suppression, increased release of iron into the circulation and decrease of iron stores.
Alterations in iron metabolism can have immunomodulatory effects. The intra cellular iron content in macropahges and monocytes, has shown pro-inflammatory effects in several investigations. Hepcidin is reported to have pro-inflammatory effects in some reports, and anti-inflammatory effects in others.
Although phlebotomy is routinely performed in blood donors, and seemingly does not have significant health risks, it is highly relevant to know what the effect of phlebotomy is on immunity. Alterations in immunity due to phlebotomy could have beneficial effects, like the suppression of the low grade inflammatory process that contributes to atherosclerosis, but in theory could also contribute to a suppressed innate immune response that could increase the risk of infection. This is not only relevant for blood donors, but also for patients suffering from blood loss and for daily clinical practice in which blood is routinely drawn of patients for laboratory determinations.
Objective: To assess the ex vivo cytokine production of whole blood during 28 days after phlebotomy (routine withdrawal of 500 ml of blood).
Study design: Intervention study in 10 healthy male volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age >18 and <36 years
- •Healthy as concluded from medical history
排除标准
- •Having donated blood to the blood bank within one year preceding phlebotomy
- •Significant blood loss from trauma within one year preceding phlebotomy
- •Having lost > 100 ml of blood due to any cause, within 3 months preceding phlebotomy (not counting blood withdrawn during screening visit)
- •Having lost > 50 ml of blood due to any cause, within 1 month preceding phlebotomy (not counting blood withdrawn during screening visit)
- •Having lost >20 ml blood due to any cause, within 1 week preceding phlebotomy (not counting blood withdrawn during screening visit)
- •Family history of thallasemia, sickle cell disease, hereditary hemochromatosis, or iron refractory iron deficiency anemia
- •Signs of history of infection within 2 weeks preceding phlebotomy
- •History of frequent vasovagal response
结局指标
主要结局
ex vivo TNF-afpha production of whole blood in reponse to incubation with E. Coli LPS
时间窗: 1 day before till 28 days after phlebotomy
Blood will be drawn on day -1, 0, 1, 3, 5, 7, 14, 21 and 28 after phlebotomy, to assess ex vivo cytokine production.
次要结局
- ex vivo IL6 and IL-10 production of whole blood in response to incubation with E.Coli LPS(1 day before till 28 days after phlebotomy)
- Changes in plasma hepcidin(1 day before till 28 after phlebotomy)
- Changes in other markers of iron homeostasis (serum iron, transferrin saturation, ferritin)(1 day before till 28 after phlebotomy)
- Adverse Events(1 day before till 28 after phlebotomy)
- Changes in hemoglobin, hematocrit, white blood cell count and differential(1 day before till 28 after phlebotomy)