Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)
infection can lead to a
cytokine storm, unleashed in part by pyroptosis of virus-infected macrophages and monocytes.
Interleukin-6 (IL-6) has emerged as a key participant in this ominous complication of
COVID-19.
IL-6 antagonists have improved outcomes in patients with
COVID-19 in some, but not all, studies.
IL-6 signaling involves at least 3 distinct pathways, including classic-signaling, trans-signaling, and trans-presentation depending on the localization of
IL-6 receptor and its binding partner
glycoprotein gp130.
IL-6 has become a therapeutic target in
COVID-19,
cardiovascular diseases, and other inflammatory conditions. However, the efficacy of inhibition of
IL-6 signaling in
metabolic diseases, such as
obesity and diabetes, may depend in part on cell type-dependent actions of
IL-6 in controlling lipid metabolism,
glucose uptake, and
insulin sensitivity owing to complexities that remain to be elucidated. The present review sought to summarize and discuss the current understanding of how and whether targeting
IL-6 signaling ameliorates outcomes following
SARS-CoV-2 infection and associated clinical complications, focusing predominantly on metabolic and
cardiovascular diseases.