[Humoral mediators in the pathophysiology of organ dysfunction in sepsis]

It is recognized that various humoral mediators, especially inflammatory cytokines such as tumor necrosis-factor-alpha and interleukin (IL)-1 beta, play a key role in the pathophysiology of septic shock and organ dysfunction following severe infection. We have recently begun to employ a rapid measurement system that allows us to measure blood IL-6 levels within 30 min using a chemiluminescent enzyme immunoassay. IL-6 blood levels reflect well the activation of the cytokine cascade and correlated well with the severity of patient's, condition. The ratio of simultaneously measured IL-6 blood levels in peripheral and pulmonary arteries is useful to identify the site responsible for cytokine production. Early initiation of PMMA-CHDF as a cytokine modulator of septic shock results in improved recovery from shock and in improved outcome. Genetic analysis of cytokine-related genes revealed a high frequency of a specific genotype in patients who have extremely high IL-6 blood levels. Screening of patients at high risk of hypercytokinemia with the specific genotype would enable appropriate treatments and contribute to future tailor-made medicine.