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

Rahajeng N Tunjungputri, Yang Li, Philip G de Groot, Charles A Dinarello, Sanne P Smeekens, Martin Jaeger, Marije Doppenberg-Oosting, Milou Cruijsen, Heidi Lemmers, Helga Toenhake-Dijkstra, Raul Aguirre-Gamboa, Vinod Kumar, Cisca Wijmenga, Leo A B Joosten, Mihai G Netea, Andre van der Ven, Quirijn de Mast*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

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)-1 beta pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1 beta-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1 beta-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-1 beta 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-1 beta on different levels. First, platelet number was positively associated with plasma IL-1 beta concentrations (p = 8.9 x 10(-9)) and inversely with concentrations of alpha-1-anti-trypsin (p = 1.04 x 10(-18)), which is a known antagonist of IL-1 beta. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1 beta 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-1 beta-mediated inflammation.

Original languageEnglish
Pages (from-to)2112-2125
Number of pages14
JournalThrombosis and Haemostasis
Volume118
Issue number12
DOIs
Publication statusPublished - Dec-2018

Keywords

  • platelet immunology
  • inflammation
  • infectious diseases
  • cytokines
  • platelet physiology
  • FUNCTIONAL GENOMICS APPROACH
  • ACTIVATED PLATELETS
  • CYTOKINE PRODUCTION
  • CIGARETTE-SMOKING
  • DISEASE
  • PROTEIN
  • LOCI
  • ALPHA-1-ANTITRYPSIN
  • AGGREGATION
  • INHIBITION

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