PERSISTENT ELEVATION OF INFLAMMATORY CYTOKINES PREDICTS A POOR OUTCOME IN ARDS - PLASMA IL-1-BETA AND IL-6 LEVELS ARE CONSISTENT AND EFFICIENT PREDICTORS OF OUTCOME OVER TIME

Background: Inflammatory cytokines have been related to the developmen t of adult respiratory distress syndrome (ARDS), shock, and multiple o rgan dysfunction syndrome (MODS). We tested the hypothesis that unfavo rable outcome in patients with ARDS is related to the presence of a pe rsistent inflammatory response. For this purpose, we evaluated the beh avior of inflammatory cytokines during progression of ARDS and the rel ationship of plasma inflammatory cytokines with clinical variables and outcome. Methods: We prospectively studied 27 consecutive patients wi th severe medical ARDS. Plasma levels of tumor necrosis factor alpha ( TNF-alpha) and interleukins (ILs) 1 beta, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5 , 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation, Subgroups of patients were iden tified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared f or levels of plasma inflammatory cytokines on day 1 of ARDS and over t ime.Results: Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients w ith sepsis (86 vs 38%, p<0.02). The mean initial plasma levels of TNF- alpha, IL-1 beta, IL-6, and IL-8 were significantly higher in nonsurvi vors (p<0.0001) and in those patients with sepsis (p<0.0001). Plasma l evels of IL-1 beta (p<0.01) and IL-6 (p=0.03) were more strongly assoc iated with patient outcome than cause of ARDS (p=0.8),lung injury scor e (LIS), APACHE II score, sepsis (p=0.16), shack, or MODS score. Plasm a levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 remained significantl y elevated over time (p<0.0001) in those who died. Although it was the best early predictor of death (p<0.001), plasma IL-2>200 pg/mL lost i ts usefulness after the first 48 h. A plasma IL-1 beta or IL-6 level > 400 pg/mL on any day in the first week of ARDS was associated with a l ow likelihood of survival. Conclusions: Our findings indicate that unf avorable outcome in acute lung injury is related to the degree of infl ammatory response at the onset and during the course of ARDS. Patients with higher plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 on day I of ARDS had persistent elevation of these inflammatory cytokines over time and died, Survivors had lesser elevations of plasma inflamm atory cytokines on day 1 of ARDS and a rapid reduction over time. Plas ma IL-1 beta and IL-6 levels were consistent and efficient predictors of outcome.