The role of interleukin-6 receptor in cardiovascular and cerebrovascular diseases
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Interleukin-6 receptor (IL-6R) plays a pivotal role in pathogenesis of cardiovascular and cerebrovascular diseases.
IL-6R is associated with cardiovascular and cerebrovascular diseases in cohort studies.
IL-6R will be a promising drug target in cardiovascular and cerebrovascular diseases.
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ABSTRACT
Interleukin-6 receptor (IL-6R) plays a pivotal role in Interleukin-6 (IL-6) signaling, which is an important pathogenic mechanism of cardiovascular and cerebrovascular diseases. IL-6R exists as membrane-bound and soluble forms and signals through classic, trans-, and cluster signaling that converge on JAK–STAT3, MAPK/ERK and PI3K–Akt pathways, while the IL-6 buffer system modulates signal intensity. Experimental studies show that IL-6 signaling drives acute-phase responses, dyslipidemia, endothelial activation, leukocyte recruitment, blood–brain barrier disruption, angiogenesis, and vascular remodeling. IL-6R is an important therapeutic target in inflammation, as evidenced by the approval of monoclonal antibodies like tocilizumab, sarilumab, and satralizumab. In addition, other emerging IL-6R-directed biologics and trans-signaling-selective approaches show promising anti-inflammatory activity in immune-mediated diseases. Mendelian randomization (MR) analyses using IL-6R variants as instruments indicate that partial lifelong downregulation of IL-6 signaling causally reduces the risk of coronary heart disease, ischemic stroke, abdominal aortic aneurysm, and other vascular phenotypes. Early clinical trials suggest tocilizumab has acceptable cardiovascular safety and improvements in acute inflammatory response, myocardial injury, and salvage. We propose that IL-6R might be a promising biomarker and therapeutic target for cardiovascular prevention and treatment. This review will summarize the role of IL-6R in cardiovascular and cerebrovascular diseases with reference to historical literature and discuss its potential clinical applications. Future studies should build large scale specific disease cohorts and further explore novel interventions targeting IL-6R signaling to advance the implementation of anti-inflammatory therapeutic strategies in this field. -
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REFERENCES
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Zou J., Wang Z., Jiang M., et al. (2026). The role of interleukin-6 receptor in cardiovascular and cerebrovascular diseases. The Innovation Medicine 4:100239. https://doi.org/10.59717/j.xinn-med.2026.100239
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Zou J., Wang Z., Jiang M., et al. (2026). The role of interleukin-6 receptor in cardiovascular and cerebrovascular diseases. The Innovation Medicine 4:100239. https://doi.org/10.59717/j.xinn-med.2026.100239
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Figure 1.
The three signaling modes of IL-6 and the three production mechanisms of sIL-6R.
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Figure 2.
IL-6R mediated pathological mechanisms in cardiovascular and cerebrovascular disease
