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).
Keywords: ADP, adenosine diphosphate; CAP, community-acquired pneumonia; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ELISA, enzyme-linked immunosorbent assay; FEV-1, forced expiratory volume in 1 s; HAP, hospital-acquired pneumonia; IL, interleukin; IQR, interquartile range; Kfc, capillary filtration coefficient; LPS, lipopolysaccharide; LTA, light transmission aggregometry; MPO, myeloperoxidase; MVV, maximum ventilation velocity; NE, neutrophil elastase; NET, neutrophil extracellular trap; OR, odds ratio; PRP, platelet-rich plasma; TNF, tumor necrosis factor; TRAP, thrombin receptor activating peptide; WT, wild-type; dsDNA, doubled-stranded DNA; inflammation; leukocytes; platelets; pneumonia; sepsis.