Hypercytokinemia a underlies the morbid condition of sepsis.

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In sepsis, inflammatory cytokines are produced as a local or systemic reaction, and cytokines produced locally act on distant organs. Cytokines are produced in abnormal quantities in the presence of sepsis. Cytokine production is controlled positively and negatively, and abnormal production is usually suppressed. However, when cytokines are produced in abnormal quantities as a result of a disorder of control, irreversible morbid conditions including ARDS, DIC and sepsis are induced. The most severe morbid condition is septic shock. It often progresses to multiple organ failure, frequently leading to a fatal course. In this process, phospholipase A2, eicosanoid, nitrogen monoxide, endothelin-1, thrombomodulin, neutrophil elastase, adhesion molecules, and so on are produced in response to stimulation with cytokines. They induce cytotoxicity and tissue disorder directly or indirectly, thereby leading to complicated morbid conditions. It was confirmed that neutrophils play an important role in the secondary systemic response to sepsis. The observation indicates that activation of neutrophils fixes the course of systemic sepsis to establish conditions for the development of septic shock and multiple organ failure. Our future research tasks include phenomenological elucidation of details of the general secondary systemic response, acquisition of fundamental knowledge contributing to treatment of septic shock and multiple organ failure, and construction of a theory of infection control on the basis of changes in bio-reactivity.