IL-18 is a member of IL-1 superfamily of cytokines. IL-18 is expressed by many human lymphoid and nonlymphoid cells, and has an important role in inflammatory processes. It can stimulate the NK cells and certain T cells to release IFN gamma which plays an important role in activating the macrophages or other cells. IL-18 synergistically with IL-12 contributes to Th1 differentiation and, therefore, is important in host defense mechanisms against intracellular bacteria, viruses, and fungi. The IL-18 cytokine increased expression of vascular cell adhesion molecule-1(VCAM1) and the adherence of melanoma cells. IL-18 plays a major role in atherosclerotic plaque destabilization leading to acute ischemic syndromes. IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota.