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Thromb Haemost. 2018 Dec;118(12):2112-2125. doi: 10.1055/s-0038-1675603. Epub 2018 Nov 19.

The Inter-Relationship of Platelets with Interleukin-1β-Mediated Inflammation in Humans.

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Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Center for Tropical and Infectious Diseases (CENTRID), Dr. Kariadi Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Medicine, University of Colorado Denver-Aurora, Colorado, United States.
Department of Immunology, K. G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.



 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.


 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).


 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.


 This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1β-mediated inflammation.

[Indexed for MEDLINE]

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