Skip to main content

Dipyridamole modulates the innate immune response during human endotoxemia


Previous studies have shown that the endogenous nucleoside adenosine is able to modulate inflammation and to prevent associated organ injury. Dipyridamole, an adenosine re-uptake inhibitor, increases extracellular adenosine concentrations during unfavorable conditions (for example, inflammation), and as such may modulate the inflammatory response. We examined the effects of dipyridamole treatment on innate immunity during human experimental endotoxemia.


In a randomized double-blind placebo-controlled study, 20 healthy subjects received 2 ng/kg Escherichia coli endotoxin intravenously following 7-day pretreatment with dipyridamole, 200 mg retard twice daily, or placebo.


Nucleoside transporter activity was significantly reduced by dipyridamole treatment with 89 ± 2% (P < 0.0001) and resulted in significantly augmented endogenous adenosine levels. Plasma concentrations of dipyridamole correlated with the peak adenosine concentration 2 hours after LPS administration (r = 0.82, P = 0.0038) and significantly augmented the anti-inflammatory IL-10 response during endotoxemia (P < 0.0001; Figure 1), an effect that correlated with the dipyridamole-induced increase in adenosine (r = 0.82; P = 0.0035). Finally, IL-10 peak concentrations were associated with a more pronounced decline in TNFα (r = 0.54, P = 0.018).

Figure 1
figure 1

Cytokine response following endotoxemia.


Dipyridamole treatment increases adenosine concen-trations during systemic inflammation associated with an augmented anti-inflammatory response and a faster decline in TNFα during human experimental endotoxemia.

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Ramakers, B., Riksen, N., Stal, T. et al. Dipyridamole modulates the innate immune response during human endotoxemia. Crit Care 15 (Suppl 1), P266 (2011).

Download citation

  • Published:

  • DOI:


  • Dipyridamole
  • Nucleoside Transporter
  • Extracellular Adenosine
  • Adenosine Concentration
  • Endogenous Adenosine