IL-18, a pro-inflammatory cytokine, correlates with the severity of sepsis through IL-18R interaction,[8,9] which activates Th1 cells and induces IFN-γ production via NF-κB.[10,11] IL18RAP enhances IL-18/IL-18R binding, further boosting IFN-γ production, seen in sepsis.[12,13] IFN-γ and TNF-α stimulate iNOS in macrophages, producing nitric oxide (NO), which triggers vasodilation and hypotension by activating soluble guanylyl cyclase (sGC) in arterial endothelial cells.[14, 15, 16, 17, 18] The mechanism was summarized in the Figure 7I. This evidence concerns the gene NFKB1 and Sepsis.