ACUTE LUNG INJURY

Extracellular thioredoxin levels are increased in patients with acute lung injury

M E Callister¹, A Burke-Gaffney¹, G J Quinlan¹, A G Nicholson², R Florio², H Nakamura³, J Yodoi⁴, T W Evans¹

¹ Unit of Critical Care, National Heart and Lung Institute Division, Imperial College Faculty of Medicine, Royal Brompton Hospital, London, UK
² Department of Histopathology, Royal Brompton Hospital, London, UK
³ Department of Experimental Therapeutics, Translational Research Center, University of Kyoto, Kyoto, Japan
⁴ Department of Biological Responses, Institute of Virus Research, University of Kyoto, Kyoto, Japan

Correspondence to:
Professor T W Evans
Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK; T.Evans{at}rbht.nhs.uk

Background: Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult.

Methods: Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n = 30) and healthy controls (n = 18, plasma; n = 14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n = 10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores.

Results: BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9–132.9) v 16.0 ng/ml (IQR 8.9–25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin.

Conclusions: Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.

Abbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; BAL, bronchoalveolar lavage; IL, interleukin; Trx, thioredoxin

Keywords: acute lung injury; acute respiratory distress syndrome; interleukin-8; inflammation; thioredoxin

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