Background-Obliterative bronchiolitis (OB) remains an impediment to long-term survival after lung transplantation. IL-1 beta (IL-1Β) has been studied as proinflammatory and profibrotic factor in allograft chronic lung tissue rejection. IL-1 receptor antagonist (IL-1rn) is competitive inhibitor to IL-1Β and mediates the anti-inflammatory and antifibrotic effects of mesenchymal stem cells during lung injury. We hypothesized that IL-1rn overexpression prevents the progression of OB in an established heterotopic tracheal transplantation model.

Methods-Tracheas from BALB/c mice were implanted and wrapped in the omentum of BALB/c (isografts), C57BL/6 (allografts), IL-1rn overexpression (IL-1rn+/+), IL-1rn knock out (IL-1rn-/-) mice. The tracheas explanted after 21 days were evaluated histologically, and real time-polymerase chain reaction (PCR) for IL-1rn, IL-1Β, IL-1 alpha (IL-1Α) mRNA levels. Cytokine quantification for IL-1 rn, IL-1Β, IL-1Α proteins in plasma samples was done by enzyme linked immunosorbent assay (ELISA) 21 days after surgery.

Results-IL-1rn overexpression mice showed significant reduction of the tracheal luminal occlusion compared to control allograft animals (p<0.0001). The gene expression of IL-1rn in tracheal tissue explanted from IL-1rn overexpression animals was increased (50-150 fold) as compared to tissue from control isograft, allograft and IL-1rn knock out animals (p<0.0001).

There was also significant increase in plasma IL-1rn levels in the IL-1rn +/+ animals as compared to other groups (p<0.0001).

Conclusions-The results suggest that IL-1rn overexpression protects against experimental OB. These findings provide new insights into the mechanisms of lung chronic rejection and may lead to new strategy for the treatment of OB.

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