Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure.

The clinical presentation of patients with multiorgan failure caused by septic conditions is very similar to that seen in patients with multiorgan failure after cardiopulmonary bypass. It has been hypothesized that the same mechanisms are at work in both instances. This commonality of presentation and mechanisms is denoted by the new term systemic inflammatory response syndrome. The systemic inflammation resulting from cardiopulmonary bypass is manifested by the development of adult respiratory distress syndrome. Overall mortality for this condition is high, and the absence of a specific therapy reflects the lack of understanding of the mechanisms involved. The risk factors associated with multiorgan failure include the age of the patient, the number of failed organs, and whether these organ failures persist or resolve. The release of a variety of inflammatory mediators has been implicated in the pathogenesis of sepsis. These include the cytokines (tumor necrosis factor, interleukin-1, interleukin-6), lipid and arachidonate metabolites, platelet-activating factor, and activation of the coagulation cascade. There seems to be marked synergy between these different mediators, suggesting that a combination of small amounts of them all may be more toxic than a large release of one by itself. During cardiopulmonary bypass, increased levels of circulating endotoxin have been associated with the activation of the complement system and increased levels of tumor necrosis factor. Interleukin-6 level has been shown to be elevated during bypass. The action of the inflammatory mediators to induce injury may be related to the activation of leukocytes and endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)