Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia

Autor: Susan S. Smyth, Richard Charnigo, Olga A. Vsevolozhskaya, Tracy Macaulay, Guoying Zhang, Travis R. Sexton, Zhenyu Li, Leigh Ann Callahan
Rok vydání: 2018
Předmět:
0301 basic medicine
HAP
hospital-acquired pneumonia
MPO
myeloperoxidase
030204 cardiovascular system & hematology
Gastroenterology
Pulmonary function testing
sepsis
PRP
platelet-rich plasma
0302 clinical medicine
P2Y12
NET
neutrophil extracellular trap
Kfc
capillary filtration coefficient
LTA
light transmission aggregometry
TNF
tumor necrosis factor
FEV-1
forced expiratory volume in 1 s
CAP
community-acquired pneumonia
ELISA
enzyme-linked immunosorbent assay
3. Good health
medicine.anatomical_structure
platelets
LPS
lipopolysaccharide
medicine.symptom
Cardiology and Cardiovascular Medicine
Ticagrelor
medicine.drug
medicine.medical_specialty
dsDNA
doubled-stranded DNA
leukocytes
CLINICAL RESEARCH
Inflammation
Lung injury
Sepsis
03 medical and health sciences
MVV
maximum ventilation velocity
Internal medicine
medicine
pneumonia
NE
neutrophil elastase
TRAP
thrombin receptor activating peptide
IQR
interquartile range
Lung
business.industry
medicine.disease
WT
wild-type
ADP
adenosine diphosphate
respiratory tract diseases
IL
interleukin
CI
confidence interval
OR
odds ratio
Pneumonia
030104 developmental biology
COPD
chronic obstructive pulmonary disease
inflammation
business
Zdroj: JACC: Basic to Translational Science
ISSN: 2452-302X
Popis: Visual Abstract
Highlights • As expected, ticagrelor reduced ex-vivo ADP-induced aggregation in patients with pneumonia compared with placebo. • Ticagrelor reduced platelet–leukocyte interactions as well as plasma interleukin-6 within 24 h in patients with pneumonia compared with placebo. • Ticagrelor acutely altered NETosis biomarkers, whereas placebo had no effect. • Ticagrelor improved lung function and reduced need for supplemental oxygen in patients with pneumonia compared with placebo.
Summary 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)
Databáze: OpenAIRE
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