Platelets from patients with chronic inflammation have a phenotype of chronic IL-1β release

Background: Chronic inflammation is a cardiovascular risk factor, and interleukin-1 beta (IL-1 beta) is central to the inflammatory host response. Platelets contain the NLRP3 inflammasome and are able to translate IL-1 beta messenger RNA (mRNA) and secrete mature IL-1 beta upon activation. However, the role of a chronic inflammatory environment in platelet IL-1 beta mRNA and protein content remains unclear. Objectives: The aim of the current study was to investigate intracellular platelet IL-1 beta and IL-1 beta mRNA in a chronic inflammatory state. Methods: Sixty-five patients with stable inflammation (ie, high-sensitivity C-reactive protein within predefined margins in 2 separate measurements) were stratified according to high-sensitivity C-reactive protein levels in low (0.0-0.9 mg/L), medium (1.0-2.9 mg/L), and high (3.0-9.9 mg/L) risk groups. Platelet reactivity as well as platelet IL-1 beta protein synthesis were studied. Results: The highest risk group was characterized by a distinct cardiovascular risk profile and approximately 20% higher platelet counts. While platelet reactivity was not different, a reduction in intracellular platelet IL-1 beta mRNA and IL-1 beta protein levels was observed in the highest risk group and was linked to decreased platelet size and granularity. This signature suggests a phenotype of chronic IL-1 beta secretion and could be experimentally phenocopied by stimulation of platelets from healthy volunteers with either TRAP-6 or collagen related peptide (CRP-XL). Conclusion: Our data suggest a phenotype of chronic IL-1 beta secretion by platelets in patients with chronic sterile inflammation.