title: Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome.
abstract: To determine the relationship between airspace cytokines and cellular inflammatory responses in patients with the acute respiratory distress syndrome (ARDS), we performed bronchoalveolar lavage (BAL) in 82 prospectively identified, mechanically ventilated patients on Days 3, 7, 14, and/or 21 after the onset of ARDS. We studied the relationships between bronchoalveolar lavage fluid (BALF) cell populations and the concentrations of two potent neutrophil (PMN) chemoattractants, interleukin-8 (IL-8) and epithelial cell-derived neutrophil activator-78 (ENA-78); two potent monocyte chemoattractants, monocyte chemotactic peptide-1 (MCP-1) and macrophage inflammatory peptide-1 alpha (MIP-1 alpha); and the early response cytokine interleukin-1 beta (IL-1 beta) and its naturally occurring antagonist, IL-1 receptor antagonist protein (IRAP). We found that all of these cytokines were significantly increased regardless of the duration of ARDS. IL-8 and ENA-78 were the cytokines most strongly and consistently correlated with PMN concentrations in the lung fluids of patients with ARDS, and the correlations were independent of the other cytokines or coexisting lung infection. None of the cytokines tested correlated with macrophage concentrations. MCP-1 was directly correlated with lung injury score on Days 7, 14, and 21. Although neither IL-8 nor ENA-78 was associated with outcome, levels of IL-1 beta measured on Day 7 were associated with an increased risk of death (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.1 to 7.4). These data demonstrate potential molecular mechanisms of the persistent inflammatory process in the lungs of patients with ARDS.
authors.affiliation: Medical Research Service, Seattle VA Medical Center, Washington, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Goodman
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: D P
authors.initials: DP
authors.lastname: Martin
authors.forename: K P
authors.initials: KP
authors.lastname: Steinberg
authors.forename: J A
authors.initials: JA
authors.lastname: Milberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Maunder
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: A
authors.initials: A
authors.lastname: Walz
authors.forename: L D
authors.initials: LD
authors.lastname: Hudson
authors.forename: T R
authors.initials: TR
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016207:Cytokines / Q000302:isolation & purification*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D011237:Predictive Value of Tests; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000401:mortality
chemical_list: C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016207:Cytokines; D016209:Interleukin-8