TNF and Sepsis: Moreover, the ADAM17 substrate TNFα occurs at high levels in the blood during sepsis promoting neutrophil rigidity and the upregulation of integrin adhesion molecules, in turn causing occlusion of the microvasculature, ischemia, and tissue destruction through the release of cytotoxic factors (Brown et al., 2006; Alves-Filho et al., 2009; Lerman and Kim, 2015).