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.