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Thromb Haemost 2000; 84(03): 381-387
DOI: 10.1055/s-0037-1614032
Commentary
Schattauer GmbH

Multi-Cellular Activation In Vivo by Endotoxin in Humans – Limited Protection by Adenosine Infusion

Nailin Li
1   From the Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Stockholm
,
Anne Soop
2   Division of Anesthesiology, Department of KARO, Huddinge Hospital, Huddinge, Sweden
,
Alf Sollevi
2   Division of Anesthesiology, Department of KARO, Huddinge Hospital, Huddinge, Sweden
,
Paul Hjemdahl
1   From the Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Stockholm
› Author AffiliationsThe authors are grateful to Mrs Maud Daleskog, Pia Hillelson, Maj-Christina Johansson, Wiveca Gustavsson, and Inga Hellström for their expert technical assistance. The study was support by grants from the Swedish Medical Research Council (5930, 7485), the King Gustaf V and Queen Victoria Foundation, the Swedish Heart-Lung Foundation, the Swedish Society for Medical Research, and Item Development AB (Stockholm, Sweden).
Further Information

Publication History

Received 24 December 1999

Accepted after resubmission 04 April 2000

Publication Date:
14 December 2017 (online)

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Summary

The influence of adenosine infusion (40 µg/kg/min for 4 h) on inflammatory and hemostatic parameters was investigated in healthy males without (n = 10) or with (n = 11) intravenous endotoxin injection (4 ng/kg). Without endotoxin, adenosine elevated circulating leukocytes and circulating platelet-leukocyte aggregates. Endotoxin activated platelets and leukocytes in vivo. Platelet activation was seen as slightly increased platelet P-selectin expression, decreased platelet counts, and elevated plasma soluble P-selectin (from 39.6 ± 3.4 to 68.9 ± 6.6 ng/ml; P <0.01). Leukocyte activation was evidenced by increased CD11b expression (from MFI of 0.54 ± 0.02 to 2.21 ± 0.17; P <0.01) and plasma elastase levels (from 25.3 ± 2.5 to 169.3 ± 22.5 ng/ml; P <0.01). Endotoxin also enhanced platelet and leukocyte responsiveness to in vitro stimulation. Endotoxin induced von Willebrand factor secretion (from 92 ± 8 units to 265 ± 19 units at 4 h; P <0.001) and enhanced thrombin generation in vivo. Endotoxin induced leukocytosis and thus increased circulating platelet-leukocyte, mainly platelet-neutrophil, aggregates. Adenosine caused slight attenuation of platelet reactivity to agonist stimulation, enhanced the endotoxin-induced leukocytosis, and detained more platelet-leukocyte aggregates in circulation, but did not attenuate endotoxin-induced neutrophil elastase secretion, von Willebrand factor secretion, or thrombin generation. Thus, endotoxemia induces multi-cellular activation in vivo. Adenosine inhibits leukocyte adhesion and extravasation, and mildly attenuates platelet responsiveness and soluble P-selectin release. Adenosine has the potential of becoming a therapeutic antiinflammatory drug, but an optimal treatment strategy needs to be developed.

Key words

Adenosine - endotoxin - platelets - leukocytes - platelet-leukocyte aggregates
 

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