TNF and Sepsis: It is now well-established in polymicrobial sepsis in mice that there is an early phase of robust activation of the innate immune system (1–3 days after CLP) during which time neutrophils (PMNs) and monocytes/macrophages release powerful proinflammatory mediators (TNF, IL-6, IL-1β, IL-17, etc.)in a “cytokine burst” that causes cell damage and multiorgan dysfunction, especially affecting kidneys, heart, liver, and other organs (13, 25, 26).