Volume 15 Supplement 1

31st International Symposium on Intensive Care and Emergency Medicine

Open Access

Dipyridamole modulates the innate immune response during human endotoxemia

  • B Ramakers1,
  • NP Riksen1,
  • TH Stal1,
  • S Heemskerk1,
  • P Van den Broek1,
  • JG Van der Hoeven1,
  • P Smits1 and
  • P Pickkers1
Critical Care201115(Suppl 1):P266

https://doi.org/10.1186/cc9686

Published: 1 March 2011

Introduction

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.

Methods

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.

Results

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

Cytokine response following endotoxemia.

Conclusions

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.

Authors’ Affiliations

(1)
Radboud University Nijmegen Medical Centre

Copyright

© Ramakers et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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