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Interleukin-1 receptor antagonist as a biomarker for bronchiolitis obliterans syndrome in lung transplant recipients

2002; Wolters Kluwer; Volume: 73; Issue: 4 Linguagem: Inglês

10.1097/00007890-200202270-00020

1534-6080

John A. Belperio, Bruno DiGiovine, Michael P. Keane, Marie D. Burdick, Ying Xue, David J. Ross, Joseph P. Lynch, Steven L. Kunkel, Robert M. Strieter,

Ear Surgery and Otitis Media

Background. The major limitation to survival after lung transplantation is bronchiolitis obliterative syndrome (BOS). BOS is a chronic inflammatory/immunologic process characterized by fibroproliferation, matrix deposition, and obliteration of the airways. The mechanism(s) that lead to fibro-obliteration of allograft airways have not been fully elucidated. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring antagonist of the pro-inflammatory cytokine IL-1 and has been associated with a number of fibroproliferative diseases. Methods. We determined whether IL-1Ra, as compared to IL-1β, IL-10, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α, in the bronchoalveolar lavage fluid (BALF) from lung transplant recipients was associated with BOS. BALF was collected from three groups of patients: BOS (n=22), acute rejection (n=33), and healthy transplant recipients (n=30). Results. IL-1Ra levels were significantly elevated in patients with BOS compared to healthy lung transplant recipients and patients with acute rejection (P <0.001 and P <0.05, respectively). Furthermore, when patients with BOS had their BALF analyzed from their last bronchoscopy before the development of BOS (Future BOS [FBOS] group) (n=20), their levels of IL-1Ra were also significantly elevated compared to healthy lung transplant recipients and patients with acute rejection (P <0.001 and P <0.05, respectively). Importantly, the elevated levels of IL-1Ra in the BOS and FBOS groups were not accompanied by any significant increases in IL-1β, IL-10, TGF-β, or TNF-α. Conclusion. These findings suggest that elevated levels of IL-1Ra may be attenuating IL-1 bioactivity during the pathogenesis of BOS and creating a local environment that favors fibroproliferation and matrix deposition.