Direct Interleukin-6 Inhibition Blunts Arterial Thrombosis by Reducing Collagen-Mediated Platelet Activation

Area of Science:

• Cardiovascular Biology
• Immunology
• Hematology

Background:

• Clinical trials show anti-interleukin-6 (IL-6) therapy reduces thrombosis biomarkers in high-risk patients.
• The precise antithrombotic mechanism of direct IL-6 inhibition remains unclear.
• This study investigates how IL-6 blockade impacts arterial thrombosis and platelet function.

Purpose of the Study:

• To elucidate the effect of direct IL-6 inhibition on experimental arterial thrombus formation.
• To identify the cellular mechanisms underlying IL-6's role in thrombosis.
• To validate findings in both animal models and human patient samples.

Main Methods:

• Mice with chronic inflammation received anti-IL-6 antibody or isotype control before laser-induced carotid artery thrombosis.
• Coagulation factors and platelet reactivity were assessed in mice.
• Platelet activation was measured ex vivo in human samples treated with ziltivekimab biosimilar or control.

Main Results:

• Anti-IL-6 treatment significantly reduced thrombus formation in mice without altering coagulation factors.
• Platelet activation by collagen-related peptide was significantly blunted in mice and humans treated with anti-IL-6 therapy.
• Ex vivo ziltivekimab biosimilar treatment reduced platelet reactivity in patients with prior percutaneous coronary intervention.

Conclusions:

• Direct IL-6 inhibition effectively reduces arterial thrombus formation by inhibiting collagen-induced platelet activation.
• These findings provide a mechanistic basis for observed clinical benefits of anti-IL-6 therapy.
• The results support the ongoing clinical evaluation of ziltivekimab in cardiovascular outcome trials.