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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.

Author information

1
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Center for Tropical and Infectious Diseases (CENTRID), Dr. Kariadi Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia.
3
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
4
Department of Medicine, University of Colorado Denver-Aurora, Colorado, United States.
5
Department of Immunology, K. G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
6
Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
7
Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

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.

PMID:
30453346
DOI:
10.1055/s-0038-1675603
[Indexed for MEDLINE]

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