TNF and Sepsis: In models of hemorrhagic shock and sepsis, eCIRP can act as an important endogenous proinflammatory mediator that directly upregulates the expression of TNF-α and IL-6, triggering a waterfall response of inflammation and exacerbating tissue damage, while neutralizing antibodies of eCIRP could attenuate the inflammatory response and improve survival in hemorrhagic and septic animals [34, 35].