The Effects of Oral Dipyridamole Treatment on the Innate Immune Response During Human Endotoxemia
Status:
Completed
Trial end date:
2010-10-01
Target enrollment:
Participant gender:
Summary
During sepsis and septic shock the immune response can be overwhelming leading to excessive
tissue damage, organ failure and death. Ideally, the inflammatory response is modulated
leading to both adequate protection to invading pathogens as well as limitation of an
exuberant immune response. In the last few years adenosine is proposed to have a central role
in the modulation of inflammation. In unfavorable conditions such as hypoxia, ischemia or
inflammation adenosine is quickly up-regulated; with concentrations up to tenfold in septic
patients. Many animal studies have shown that adenosine is able to attenuate the inflammatory
response and decrease mortality rates. Therefore, pharmacological elevation of the adenosine
concentration is an potential target to attenuate inflammation and limit organ injury.
Dipyridamole, an adenosine re-uptake inhibitor is able to increase the adenosine
concentration and limit ischemia-reperfusion injury. In order to study the effects of
dipyridamole on the inflammatory response we aim to use the so called human endotoxemia
model. This model permits elucidation of key players in the immune response to a gram
negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel
therapeutic strategies in a standardized setting.