Is Interleukin-38 a key player cytokine in atherosclerosis immune gene therapy?

Abstract

Atherosclerosis, a chronic inflammatory disease of the arteries associated with lipids and other metabolic alterations is a leading cause of death all around the world and its rate is raising as a result of unhealthy lifestyles. Reports by World Health Organization indicate that 31% of all death occurrences are due to heart attacks and strokes. Today, the most common medicines for treating atherosclerosis are statins which are HMG-coA reductase inhibitors. Beside their benefits in treating atherosclerosis, some side effects have been reported as well. Thus, therapeutic methods based on statins should be evaluated to result in more beneficial effects. Since atherosclerosis is an inflammatory disorder, an anti-inflammatory component can decrease the impact of this disease. Interleukin-38, a newly discovered anti-inflammatory cytokine, which acts as an Interleukin-36 receptor antagonist can block Nuclear Factor KB and Activator protein-1 signaling pathways, and block atherogenic core formation accordingly. This novel proposed immune gene therapy can be applied to atherosclerosis treatment in a trial study. In this hypothesis, Interleukin-38 gene is transferred into bone marrow Mesenchymal Stem Cells of atherosclerotic mouse model Apo E-/- via an adenoviral vector. It is expected that Interleukin-38 gene expression by Mesenchymal Stem Cells can efficiently remedy atherosclerosis without the side effects of statins.