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]. This evidence concerns the gene TNF and systemic inflammatory response syndrome.