Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches to reduce complications. (Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor [XANTHIPPE]; NCT01883869)

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Published in JACC: Basic to Translational Medicine, v. 3, no. 4, p. 435-449.

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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This work was supported by an investigator-initiated grant from AstraZeneca as well as an R01 from the National Institutes of Health National Heart, Lung, and Blood Institute HL123927. Drs. Smyth and Charnigo have been principal investigators and coinvestigators on AstraZeneca grants, including the one funding this work.

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For supplemental figures, please see the online version of this paper.

1-s2.0-S2452302X18301293-mmc1.pdf (437 kB)
Supplemental Figures 1 and 2.