ショックと臓器障害の病態におけるサイトカインの役割

DOI 被引用文献12件

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  • The role of cytokines in the pathogenetic mechanisms of shock and organ dysfunction.

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Host response to a variety of severe clinical insults is the main pathogenetic factor causing shock and organ dysfunction seen in critically ill patients, and cytokines are known to play a central role in the pathogenetic mechanisms. Of various cytokines, tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1) are the primary proinflammatory cytokines inducing the systemic inflammatory response syndrome, shock and organ dysfunction. TNF-alpha and IL-1 induce the production of themselves, IL-6, IL-8, and other endogenous mediators including platelet activating factor and nitric oxide. Infusion of recombinant TNF-alpha and/or IL-1-beta into rabbits results in the development of hypotension and an increase in cardiac output. The animals also develop pathological changes in the lungs similar to ARDS after the cytokine administration. Ibuprofen blocks these changes. These are the direct evidences supporting the hypothesis that the host response to insults, rather than an insult itself, causes shock and organ dysfunction. IL-6 acts as an alarm hormone inducing systemic acute phase responses, and IL-8 is a primary chemotactic and activating factor for granulocytes which subsequently produces various mediators including cytokines. In critically ill patients, elevated blood levels of cytokines, particularly of IL-6, have been observed. Under overwhelming insults such as sepsis, the systemic cytokine production is dysregulated resulting in the development of autodestructive systemic inflammation associated with high blood levels of various proinflammatory and anti-inflammatory cytokines. This condition is called “cytokine storm”. The improved understanding of the pathogenetic role of cytokines in acute phase response provide a rationale for the anticytokine therapies. In human trial, Anti-TNF antibody, soluble TNF receptor, or interleukin-1 receptor antagonist have shown favourable results when used in extremely severe patients. Further understanding of the mechanisms will suggest new therapeutic strategies for interrupting the cytokine storm.

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