DEPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-6, AND INTERLEUKIN-10 PRODUCTION - A REACTION TO THE INITIAL SYSTEMIC HYPERACTIVATION IN SEPTIC SHOCK

Sepsis remains a major cause of mortality in surgical intensive care u nits. Patients who survive the initial shock phase but die weeks later from multiple organ dysfunction still are a challenge to basic and cl inical research. We addressed whether fulminant sepsis results in rapi d changes (24 h) in the cellular capacity to produce cytokines in whol e blood of septic patients on further stimulation after the initial sy stemic inflammatory response. Interleukin (IL)-6 plasma concentrations from 279 pg/mL to 5979 pg/mL confirmed the presence of a systemic inf lammatory response. Anti-inflammatory IL-10 concentrations up to 275 p g/mL were detected, but there was no biologically active tumor necrosi s factor-alpha (TNF alpha) detectable (by bioassay) at the time of inv estigation. On stimulation with Escherichia coli ex vivo, proinflammat ory TNF alpha (130 pg/mL), IL-6 (4061 pg/mL), and antiinflammatory IL- 10 (711 pg/mL) production were markedly depressed in all patients comp ared with controls (2339 pg/mL, 50,319 pg/mL, and 9654 pg/mL, respecti vely). Septic shock resulted in early depression of the capacity for p ro-and anti-inflammatory cytokine production. Monitoring of this effec t, including its relationship to outcome, may offer a target variable for therapeutic efforts to maintain or restore adequate immune reactio ns to improve survival.