Cytokine Balance in the Lungs of Patients with Acute Respiratory Distress Syndrome

TLDR

ARDS is characterized by a vigorous inflammatory response in the lungs, with both pro‑ and anti‑inflammatory cytokines accumulating in bronchoalveolar lavage fluid. The study aimed to assess how the balance of pro‑ and anti‑inflammatory mediators in the lungs shifts before and after ARDS onset. Serial bronchoalveolar lavage was performed on 23 at‑risk and 46 established ARDS patients, and immunoassays and bioassays quantified cytokines, receptors, and antagonists such as TNF‑α, IL‑1β, IL‑6, and IL‑10. Cytokine levels rose before and after ARDS onset, but receptor and antagonist increases were greater, causing agonist/antagonist ratios to drop sharply at onset and remain low for at least seven days, indicating an early anti‑inflammatory response that limits net lung inflammation.

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.