Extracellular thioredoxin levels are increased in patients with acute lung injury

Matthew E Callister ¹, Anne C Burke-Gaffney ², Gregory J Quinlan ², Andrew Nicholson ³, Richard Florio ³, Hajime Nakamura ⁴, Junji Yodoi ⁴ and Timothy Evans ^4*

¹ Royal Brompton Hosptial, United Kingdom
² Imperial College, United Kingdom
³ Royal Brompton Hospital, United Kingdom
⁴ Institute of Virus Research, Japan

^* To whom correspondence should be addressed. E-mail: t.evans{at}rbht.nhs.uk.

Accepted 29 January 2006

Abstract

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 dependant upon the nature of the precipitating insult.

Methods: Bronchoalveolar lavage fluid (BALF) and plasma samples were collected from patients with ALI (n=30); healthy controls (n=18, plasma; n=14, BALF). 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. IL-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores.

Results: In patients with ALI, BALF thioredoxin concentrations were higher (median value 61.6ng/ml, IQR 34.9-132.9) than in controls (median value 16.0ng/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. BALF thioredoxin levels correlated with BALF IL-8, but neither with severity of illness scores, nor mortality. BALF 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 demonstrate a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.

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

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