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The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans
- Source :
- Thrombosis and Haemostasis, 118, 2112-2125, Thrombosis and Haemostasis, 118(12), 2112-2125. GEORG THIEME VERLAG KG, Thrombosis and Haemostasis, 118, 12, pp. 2112-2125
- Publication Year :
- 2018
-
Abstract
- Background Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1β pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1β-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation—and especially IL-1β—in a cohort of healthy volunteers. Methods We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1β and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS). Results Platelets were associated with IL-1β on different levels. First, platelet number was positively associated with plasma IL-1β concentrations (p = 8.9 × 10−9) and inversely with concentrations of α-1-anti-trypsin (p = 1.04 × 10−18), which is a known antagonist of IL-1β. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1β and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases. Conclusion This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1β-mediated inflammation.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_treatment
Interleukin-1beta
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Anti-Inflammatory Agents
LOCI
PROTEIN
infectious diseases
DISEASE
Cohort Studies
Platelet degranulation
Platelet
Cells, Cultured
platelet immunology
ALPHA-1-ANTITRYPSIN
platelet physiology
Interleukin
Antibodies, Monoclonal
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Hematology
3. Good health
FUNCTIONAL GENOMICS APPROACH
Cytokine
Coagulation
Cardiovascular Diseases
Female
medicine.symptom
Adult
Blood Platelets
Genotype
INHIBITION
Inflammation
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Antibodies, Monoclonal, Humanized
Polymorphism, Single Nucleotide
03 medical and health sciences
Young Adult
All institutes and research themes of the Radboud University Medical Center
medicine
Humans
Platelet activation
Blood Coagulation
business.industry
Platelet Count
ACTIVATED PLATELETS
CYTOKINE PRODUCTION
AGGREGATION
Platelet Activation
cytokines
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
030104 developmental biology
inflammation
Immunology
CIGARETTE-SMOKING
business
Ex vivo
Subjects
Details
- Language :
- English
- ISSN :
- 03406245
- Volume :
- 118
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....73edac121048809b7e311e9c1d6b998f