IL-38 in modulating hyperlipidemia and its related cardiovascular diseases

•IL-38 has been shown to play an important role in modulating the pathogenesis of hyperlipidemia.•IL-38 inhibits the CD4 positive T lymphocyte into Th-17 which enhance the immunosuppressive activity of the T-reg.•IL-38 suppresses the expression of inflammatory factors through the MAPK signaling pathway.•IL-38 may be a potential disease biomarker and a new therapeutic target for hyperlipidemia. Hyperlipidemia is confirmed to be associated with several health problems that include the combination of diabetes mellitus, obesity, and hypertension, ie, metabolic syndrome. Although the lipid-lowering therapy is an effective treatment in hyperlipidemia and its related cardiovascular diseases (CVDs), the persistence of high atherosclerotic risk is notable which could not be simply explained as a phenomenon of hyperlipidemia. Concerning on this notion, it is imperative to identify novel biomarkers which could monitor treatment and predict adverse cardiovascular events. It is demonstrated that the chronic inflammatory response caused by immune cells is a characteristic of hyperlipidemia and atherosclerosis. Notably, among several inflammatory related cytokines, interleukin 38 (IL-38), as a member of the IL-1 family, plays an important role in anti-inflammatory response by binding with its receptor which inhibits the downstream signaling pathways. In addition, IL-38 suppresses the expression of inflammatory factors mainly through the mitogen-activated protein kinase (MAPK). At the cellular level, IL-38 could inhibit the CD4 positive T lymphocyte into T-helper 17 (Th-17) lymphocyte which further enhances the immunosuppressive activity of the T-regulatory lymphocyte (T-reg) to inhibit the inflammatory response. Consistently, IL-38 is shown to be strongly correlated to development of hyperlipidemic related CVDs. In this review, the roles of IL-38 in the development of hyperlipidemia are fully summarized. Furthermore, a theoretical basis for further in-depth research of IL-38 for treatment of hyperlipidemia is also provided.