Overexpression of IL-1 Receptor Antagonist Attenuates Obliterative Bronchiolitis in Murine Tracheal Transplant Model

Purpose 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 and Materials 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-PCR for IL-1rn, IL-1β, IL-1 alpha (IL-1α) mRNA levels. Cytokine quantification for these proteins in plasma samples was done by ELISA 21 days after surgery. Results IL-1rn overexpression mice showed significant reduction of the tracheal luminal occlusion compared to control allograft animals (p figure 1 ] There was also significant increase in plasma IL-1rn levels in the IL-1rn +/+ animals as compared to other groups (p 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.