TNF and Sepsis: Circulating mediators such as endotoxin, other proinflammatory agents (tumor necrosis factor-a, serotonin, and histamine) or neurotoxic factors are probably released during sepsis or systemic inflammatory response syndrome, and have been proposed in the pathogenesis of CIP, but their role remains controversial because CIP can occur in the absence of an identifiable circulating mediator [31].