Reader Response: Circulating Interleukin-6 Levels and Incident Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Studies
Vinod KGupta, Physician-Medical Director, GUPTA MEDICAL CENTRE, MIGRAINE-HEADACHE INSTITUTE, S-407, Greater Kailash-Part Two, New Delhi, INDIA-110048
Submitted January 04, 2022
The study by Papadopoulos et al. presents a linear association between higher levels of circulating interleukin (IL-6) in the general population and higher long-term risk of incident ischemic stroke.1 These researchers underscore that ischemic stroke risk propensity conferred by elevated IL-6 values is independent of conventional vascular risk factors, implausibly dissociating IL-6 from atherosclerosis.
Vascular inflammation plays a critical role in predominantly age-related atherosclerosis, for which innate and adaptive immune responses are also important.2 In mice, ageing is associated with elevated levels of the inflammatory cytokine IL-6 in the aorta, which participates in a positive feedback loop with the impaired vascular mitochondrial function to accelerate atherogenesis.2 Furthermore, IL-1β and other IL-1 family cytokines are important vascular and systemic inflammatory mediators.3 Cholesterol accumulation in myeloid cells activates the NLRP3 inflammasome, which enhances neutrophil accumulation and neutrophil extracellular trap formation in atherosclerotic plaques.4 IL family, high-sensitivity C-reactive protein, and high-density lipoprotein cholesterol can predict future cardio- and cerebrovascular events, but none of these laboratory indices can be dissociated from atherosclerosis.
Hyperfocus on “independence” probably arises from popular use of monoclonal antibodies in atherosclerosis, a biologically implausible situation that challenges a broader clinical commonsense.5
Disclosure
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Papadopoulos A, Palaiopanos K, Björkbacka H, et al. Circulating Interleukin-6 Levels and Incident Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Studies [published online ahead of print, 2021 Dec 30]. Neurology. 2021;10.1212/WNL.0000000000013274. doi:10.1212/WNL.0000000000013274
Tyrrell DJ, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nat Rev Cardiol. 2021;18(1):58-68. doi:10.1038/s41569-020-0431-7
Grebe A, Hoss F, Latz E. NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. Circ Res. 2018;122(12):1722-1740. doi:10.1161/CIRCRESAHA.118.311362
Westerterp M, Fotakis P, Ouimet M, et al. Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis, and Atherogenesis. Circulation. 2018;138(9):898-912. doi:10.1161/CIRCULATIONAHA.117.032636
Gupta VK. Inflammation in atrial fibrillation and atherosclerosis: pearls and pitfalls in the theorising process. Int J Clin Pract. 2006;60(4):495-498. doi:10.1111/j.1368-5031.2006.0827a.x
The study by Papadopoulos et al. presents a linear association between higher levels of circulating interleukin (IL-6) in the general population and higher long-term risk of incident ischemic stroke.1 These researchers underscore that ischemic stroke risk propensity conferred by elevated IL-6 values is independent of conventional vascular risk factors, implausibly dissociating IL-6 from atherosclerosis.
Vascular inflammation plays a critical role in predominantly age-related atherosclerosis, for which innate and adaptive immune responses are also important.2 In mice, ageing is associated with elevated levels of the inflammatory cytokine IL-6 in the aorta, which participates in a positive feedback loop with the impaired vascular mitochondrial function to accelerate atherogenesis.2 Furthermore, IL-1β and other IL-1 family cytokines are important vascular and systemic inflammatory mediators.3 Cholesterol accumulation in myeloid cells activates the NLRP3 inflammasome, which enhances neutrophil accumulation and neutrophil extracellular trap formation in atherosclerotic plaques.4 IL family, high-sensitivity C-reactive protein, and high-density lipoprotein cholesterol can predict future cardio- and cerebrovascular events, but none of these laboratory indices can be dissociated from atherosclerosis.
Hyperfocus on “independence” probably arises from popular use of monoclonal antibodies in atherosclerosis, a biologically implausible situation that challenges a broader clinical commonsense.5
Disclosure
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References