Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review)

Niculet, Elena; Chioncel, Valentin; Elisei, Alina M.; Miulescu, Magdalena; Buzia, Olimpia D.; Nwabudike, Lawrence C.; Craescu, Mihaela; Draganescu, Miruna; Bujoreanu, Florin; Marinescu, Elisabeta; Arbune, Manuela; Radaschin, Diana Sabina; Bobeica, Carmen; Nechita, Aurel; Tatu, Alin L.

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.