Insights into Release of Interleukin-1β from Platelets

Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase

Platelets are key players in the crosstalk between inflammation and thrombosis. Therefore, insights that elucidate the mechanisms of platelet-dependent thromboinflammation are of high interest. Interleukin 1β (IL-1β) is mainly involved in NLRP3 inflammasome complex formation. IL-1β has been found to be an attractive target to suppress chronic vascular inflammation, thus improving prognosis in atherosclerotic disease.[1] Although controversial data exist, it has been proposed that resting platelets contain relevant amounts of preformed IL-1β. Besides their effects on inflammatory cells, IL-1 receptor and IL-1β play a role in megakaryocyte maturation and platelet activation.[2] The work by Pennings et al published in this issue adds to the current knowledge by shedding light on the mechanism of IL-1β release from platelets.[3] The authors convincingly demonstrated that preformed IL-1β protein can be released shortly within minutes after activation of platelets by ADP, protease-activated receptor (PAR)1, and PAR4-activating peptides. The process of IL-1β significantly correlated with the degree of platelet activation. Release of IL-1β was independent of extracellular NLRP3 activation as indicated by missing signals on NLRP3 expression/phosphorylation and caspase-1 activation. Still, it is unclear based on the performed ELISA experiments whether the protein is pro-IL-1β or mature-IL-1β and whether NLRP3 or caspase-1 is involved in the formation of intracellular pro-IL-1β. Although repeatedly demonstrated that platelets despite being anucleate are capable of de-novo protein synthesis, the question about the source of intraplatelet IL-1β is still a matter of debate. The potential translational aspects of the findings warrant further investigation. Besides the role of IL-1β inflammasome activation for leukocyte production and recruitment in atherosclerosis,[4] what is the function of inflammasome-independent platelet IL-1β? Are the detected concentrations high enough to convey substantial cellular signals and to promote alterations in the vascular environment? Experiments in mouse models indicate that IL-1β can induce thrombocytosis, suggesting that platelets could support an inflammatory feedback loop by amplifying IL-1 signaling and triggering platelet biogenesis.[5] Whether platelet-derived IL-1β contributes to this loop in the human system and what clinical impact targeting platelet IL-1β might have require deeper insight.

Conflict of Interest

None declared.

• References

• 1 Ridker PM, Everett BM, Thuren T. et al; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377 (12) 1119-1131
• 2 Beaulieu LM, Lin E, Mick E. et al. Interleukin 1 receptor 1 and interleukin 1β regulate megakaryocyte maturation, platelet activation, and transcript profile during inflammation in mice and humans. Arterioscler Thromb Vasc Biol 2014; 34 (03) 552-564
• 3 Pennings GJ, Reddel CJ, Traini M. et al. Rapid release of interleukin-1β from human platelets is independent of NLRP3 and caspase. Thromb Haemost 2022; 122 (04) 517-528
• 4 Hettwer J, Hinterdobler J, Miritsch B. et al. Interleukin-1β suppression dampens inflammatory leukocyte production and uptake in atherosclerosis. Cardiovasc Res 2021; DOI: 10.1093/cvr/cvab337.
• 5 Kimura H, Ishibashi T, Shikama Y. et al. Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible implication of IL-6. Blood 1990; 76 (12) 2493-2500

Publication History

Received: 27 October 2021

Accepted: 28 October 2021

Accepted Manuscript online:
01 November 2021

Article published online:
17 January 2022