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Inflammatory Cytokines in the BAL of Patients With ARDS
Abstract
Background Inflammatory cytokines (ICs) are important modulators of injury and repair. ICs have been found to be elevated in the BAL of patients with both early and late ARDS. We tested the hypothesis that recurrent injury to the alveolocapillary barrier and amplification of intra-alveolar fibroproliferation observed in nonresolving ARDS is related to a persistent inflammatory response. For this purpose, we obtained serial measurements of BAL IC and correlated these levels with lung injury score (LIS), BAL indexes of endothelial permeability (albumin, total protein [TP]), and outcome.Methods We prospectively studied 27 consecutive patients with severe medical ARDS. Using enzyme-linked immunosorbent assay methods, levels of tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL) 1 beta, 2, 4, 6, and 8 were measured at frequent intervals in both plasma and BAL. In 22 patients, bilateral BAL was obtained on day 1 of ARDS and at weekly intervals when possible. Right and left BALs were analyzed separately for IC levels, total cell count and differential, albumin, TP, and quantitative bacterial cultures.Results On day 1 of ARDS, the 10 nonsurvivors had significantly higher (p = 0.0002) BAL TNF-alpha, IL-1 beta, IL-6, and IL-8 levels, which remained persistently elevated over time, indicating a continuous injury process. In contrast, the 12 survivors had a lesser elevation and a rapid reduction over time. Initial BAL IL-2 and IL-4 levels were significantly higher in patients with sepsis (p = 0.006); both increased over time in survivors and nonsurvivors. BAL levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 correlated with BAL albumin and TP concentrations but not with LIS or ratio of arterial oxygen tension to inspired oxygen concentration. BAL: plasma ratios were elevated for all measured cytokines, suggesting a pulmonary origin. On day 1 of ARDS, nonsurvivors had significantly higher (p = 0.04) BAL: plasma ratios for TNF-alpha, IL-1 beta, IL-6, and IL-8. Over time, BAL:plasma ratios for TNF-alpha, IL-1 beta and IL-6 remained elevated in nonsurvivors and decreased in survivors.Conclusions Our findings indicate that an unfavorable outcome in ARDS is associated with an initial, exaggerated, pulmonary inflammatory response that persists unabated over time. Plasma IC levels parallel changes in BAL IC levels. The BAL:plasma ratio results suggest, but do not prove, a pulmonary origin for IC production. BAL TNF-alpha, IL-1 beta, and IL-8 levels correlated with BAL indices of endothelial permeability. In survivors, reduction in BAL IC levels over time was associated with a decline in BAL albumin and TP levels, suggesting effective repair of the endothelial surface. These findings support a causal relationship between degree and duration of lung inflammation and progression of fibroproliferation in ARDS.
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“The cells of innate immunity (macrophages and neutrophils) increase in number and activation, which causes the alveolar concentration of molecules related to the host stress response to increase.”
From The microbiome and critical illness (2016) · cites this paper as [117]
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Metadata
- Authors
- Meduri, G. U., Kohler, G., Headley, S., Tolley, E., Stentz, F., & Postlethwaite, A.
- Affiliations
- University of Tennessee Health Science Center (US)
- Memphis VA Medical Center (US)
- Corresponding author
- Meduri, G. Umberto
- Venue
- Chest
- Publisher
- Elsevier BV
- Published
- 1995-11
- Volume
- 108
- Issue
- 5
- Pages
- 1303-1314
- ISSN
- 0012-3692 (ISSN-L)
- OpenAlex
- W2153354364
- Cited by
- 695
- References
- 72
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 14 · 2023: 23 · 2022: 44 · 2021: 47 · 2020: 51 · 2019: 19 · 2018: 12 · 2017: 18 · 2016: 18 · 2015: 23 · 2014: 16 · 2013: 21 · 2012: 20
- FWCI
- 19.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CHEST Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (5M01RR-00211, M01RR000211)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- acute respiratory distress syndrome, inflammatory cytokines, bronchoalveolar lavage, TNF-α, interleukin-6, interleukin-8, IL-1β, interleukin-2, IL-4, endothelial permeability, sepsis, lung injury score
- MeSH terms
- Adult, Bronchoalveolar Lavage Fluid, Cell Membrane Permeability, Endothelium, Female, Humans, Inflammation, Male, Middle Aged, Predictive Value of Tests, Prognosis, Prospective Studies, Proteins, Respiratory Distress Syndrome, Cytokines, Hospital Mortality, Disease Progression
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