Anti-Inflammatory Interleukins in the Pathogenesis of Atherosclerosis

In recent years, the study of interleukins (ILs), crucial cytokines involved in inflammation, has garnered significant attention within coronary artery disease including atherosclerosis. This review provides a detailed overview of anti-inflammatory ILs, elucidating their functions within the pathogenesis of atherosclerosis. We examine aspects of all the known anti-inflammatory ILs role in atherosclerosis, the direct impact of these ILs on the inflammation; endothelial, smooth vascular cells and macrophage's function; and their interactions with signaling pathways and molecules. The potential for diagnostic possibilities and targeted drug therapy to modulate anti-inflammatory ILs activity in atherosclerosis was explored. Taken together, findings from recent studies suggest that the main pathways through which ILs exerts its anti-inflammatory effects are: (1) taking part in the regulation of cholesterol transport or oxidised low-density lipoprotein (oxLDL) phagocytosis (IL-1Ra and IL-36Ra-indirectly); (2) affecting different blood cells' participation in the inflammation (monocytes, lymphocytes, macrophages); (3) taking place in the remodelation of the arterial wall (affecting smooth muscle and endothelium cells). Overall, IL-35, IL-37, and IL-38 appear to be the most promising for modulation of signaling pathways in experimental works and could be investigated as treatment targets. Recombinant IL-10 is investigated in experimental models as therapeutic tool. IL-1Ra is started being translated into clinical practice already. IL-13 and IL-19 are the least studied. It turns out that anti-inflammatory ILs are unlikely to serve as diagnostic markers for atherosclerosis due to their limited specificity and inconsistent associations with disease progression, as well as insufficient validation in large human cohorts. Moreover, key challenges related to delivery, dosing, and safety remain unresolved.