Connor Webb: IL-6 as a Primer of Platelet Hyperresponsiveness
Connor Webb, PHD Student at The University of Bristol, shared on LinkedIn about a recent article he and his colleagues co-authored, published in Cells MDPI, adding:
”One year ago, Jordan Vautrinot, Ingeborg Hers and I published our review proposing IL-6 as a primer of platelet hyperresponsiveness involved in cardiovascular and inflammatory diseases.
We argued that IL-6 trans-signalling via gp130, with selective crosstalk into the GPVI/collagen pathway, offered a mechanistically plausible explanation for why IL-6 is repeatedly invoked as a potential thrombo-inflammatory factor across a range of inflammatory conditions and complications (from COVID-19 to stent thrombosis).
Since then, there has been some great experimental work that directly evaluated several of the mechanisms we proposed.
Ministrini and colleagues (2025; ATVB; 45:1432) showed in mice that an IL-6 antibody selectively blunted platelet reactivity to GPVI/collagen stimulation but not to PAR-1 or P2Y12, and replicated the finding ex vivo in platelets from patients at high cardiovascular risk.
New IL-6-targeted modalities continue to emerge, and in September 2025, Novartis acquired Tourmaline Bio for approximately £1B to advance the drug pacibekitug, a long-acting IL-6 antibody, for ASCVD.
Two large cardiovascular trials involving IL-6 therapy are also rapidly approaching completion.
The ZEUS trial (estimated June 2026) is evaluating ziltivekimab in patients with established ASCVD, chronic kidney disease and systemic inflammation.
ARTEMIS is a phase 3 study of ziltivekimab as an acute therapy in patients hospitalised with acute myocardial infarction.
It was satisfying seeing some of our theories confirmed, but equally, many new questions arise about the safety, selectivity, and appropriateness of IL-6 blockade alongside existing antithrombotic strategies… in such a rapidly evolving field, nothing is for certain.
If you missed our review, please have a read.”
Title: IL-6 as a Mediator of Platelet Hyper-Responsiveness
Authors: Connor Webb, Jordan Vautrinot, Ingeborg Hers
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