Multifactorial expression of IL‑6 with update on COVID‑19 and the therapeutic strategies of its blockade (Review)
Elena Niculeț, Valentin Chioncel, Alina Mihaela Elisei, Magdalena Miulescu, Olimpia Dumitriu Buzia, Lawrence Chukwudi Nwabudike, Mihaela Crăescu, Miruna Drăgănescu, Florin Ciprian Bujoreanu, Elisabeta Marinescu, Manuela Arbune, Diana Sabina Radaschin, Carmen Bobeică, Aurel Nechita, Alin Laurențiu Tatu
Abstract
Interleukin 6 (IL-6), a cytokine produced by various cells of the human body (macrophages, lymphocytes, astrocytes, ischemic myocytes, endothelial cells) has both pro-inflammatory and anti-inflammatory properties, being a key component in regulating various physiologic and pathological processes. The structure of this molecule and the receptor system it possesses are important due to the different activities that IL-6 can exert; through trans-signaling pro-inflammatory activities are mediated, while through classic signaling, IL-6 is responsible for anti-inflammatory and regenerative activities. IL-6 signaling is involved in coronary artery disease and the global COVID-19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS-CoV-2, and is also associated with smoking or obesity-classic cardiovascular risk factors which promote inflammatory states. IL-6 levels are proportionally correlated with dyslipidemia, hypertension and glucose dysregulation, and they are associated with poor outcomes in patients with unstable angina or acute myocardial infarction. IL-6 targeting for treatment development (not only) in cardiovascular disease and COVID-19 is still a matter of ongoing research, although tocilizumab has proven to be effective in reducing the proatherogenic effects of IL-6 and is suggested to improve COVID-19 patient survival.