Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1384-1388

Pulmonary Edema Fluid from Patients with Acute Lung Injury Augments In Vitro Alveolar Epithelial Repair by an IL-1-dependent Mechanism

THOMAS GEISER, KAMRAN ATABAI, PIERRE-HENRI JARREAU, LORRAINE B. WARE, JÉRÔME PUGIN, and MICHAEL A. MATTHAY

Cardiovascular Research Institute, University of California, San Francisco, California; Institut National de la Santé et de la Recherche médicale INSERM U 492, Créteil, France; Division of Medical Intensive Care, Department of Medicine, University Hospital of Geneva, Geneva, and Division of Pulmonary Medicine, University Hospital, Bern, Switzerland

Efficient alveolar epithelial repair is crucial for the restoration of the injured alveolar epithelial barrier in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). We hypothesized that pulmonary edema fluid from patients with ALI /ARDS would inhibit alveolar epithelial repair as measured in an in vitro epithelial wound-repair model using the human alveolar epithelial-like cell line A549. In contrast to our initial hypothesis, pulmonary edema fluid from patients with ALI/ARDS increased alveolar epithelial repair by 33 ± 3% compared with pooled plasma from healthy donors (p < 0.01). By contrast, the plasma and the pulmonary edema fluid from patients with hydrostatic pulmonary edema, and the plasma from patients with ALI/ARDS had similar effects on epithelial repair as pooled plasma from healthy donors. Inhibition of interleukin-1 (IL-1) activity by IL-1 receptor antagonist reduced alveolar epithelial repair induced by ALI/ARDS edema fluid by 46 ± 4% (p < 0.001), indicating that IL-1 contributed significantly to the increased epithelial repair. In summary, pulmonary edema fluid collected early in the course of ALI/ARDS increased alveolar epithelial repair in vitro by an IL-1-dependent mechanism. These data demonstrate a novel role for IL-1 in patients with ALI/ARDS, indicating that IL-1 may promote repair of the injured alveolar epithelium.

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