1. The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans
- Author
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Heidi Lemmers, Philip G. de Groot, Raul Aguirre-Gamboa, Cisca Wijmenga, Quirijn de Mast, Rahajeng N. Tunjungputri, Marije Doppenberg-Oosting, Mihai G. Netea, Leo A. B. Joosten, Milou Cruijsen, Helga Toenhake-Dijkstra, André J. A. M. van der Ven, Vinod Kumar, Sanne P. Smeekens, Yang Li, Martin Jaeger, Charles A. Dinarello, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Department of Health and Life Sciences
- 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 - 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.
- Published
- 2018