Abstract
Acute respiratory distress syndrome (ARDS) involves an intense inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta, and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Antigens, CD / analysis
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Antigens, CD / immunology
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Biological Assay
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Bronchoalveolar Lavage Fluid / cytology
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Bronchoalveolar Lavage Fluid / immunology
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Case-Control Studies
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Cytokines / analysis*
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Cytokines / immunology*
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Female
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Humans
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Immunoassay
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Inflammation
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Inflammation Mediators / analysis*
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Inflammation Mediators / immunology*
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Interleukin-1 / analysis*
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Interleukin-1 / immunology
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Interleukin-10 / analysis
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Interleukin-10 / immunology
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Interleukin-6 / analysis*
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Interleukin-6 / immunology*
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Lung / chemistry*
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Lung / immunology*
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Male
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Middle Aged
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Prospective Studies
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Receptors, Interleukin-1 / analysis
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Receptors, Interleukin-1 / immunology
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Receptors, Interleukin-6 / analysis
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Receptors, Interleukin-6 / immunology
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Receptors, Tumor Necrosis Factor / analysis
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Respiratory Distress Syndrome / etiology
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Respiratory Distress Syndrome / immunology*
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Respiratory Distress Syndrome / mortality
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Respiratory Distress Syndrome / pathology*
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Risk Factors
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Time Factors
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Tumor Necrosis Factor-alpha / analysis*
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Tumor Necrosis Factor-alpha / immunology*
Substances
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Antigens, CD
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Cytokines
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Inflammation Mediators
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Interleukin-1
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Interleukin-6
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Receptors, Interleukin-1
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Receptors, Interleukin-6
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor-alpha
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Interleukin-10