Interleukin-17 Tissue Expression Correlates with Severity of Acute and Chronic Allograft Rejection in Rat Orthotopic Lung Transplantation

Abstract

Purpose Lung transplantation has been established as a treatment for many severe end-stage pulmonary diseases. The outcome depends mainly on rejection and the chronic form known as bronchiolitis obliterans syndrome/obliterative bronchiolitis (OB) is considered the key impediment the long term lung transplant survival. Lung transplant rejection is associated with the production of a multitude of cytokines. IL-17, involved in both innate and adaptive immunity, is a family of six isoforms and IL-17 has a key role in the pathogenesis of alloimmune-induced autoimmunity postlung transplant. However, there is no direct evidence of specific cellular immunolocalisation in lung allograft rejection. The aim of the study was therefore to investigate cytokine expression across cellular tissue type in all lung grafts. Methods and Materials Lungs from Lewis rats were orthotopically transplanted into Fisher rats (33 cases). Histological features and tissue IL17 evaluation were assessed in the grafts scoring the immunostaining (score from 0 to 3) distinguishing different cell types: lymphocytes, macrophages, airway epithelial and endothelial cells. Results Twelve animals died early due to intraoperative bleeding (9 cases) and infections (3 cases). Acute rejection, lymphocytic bronchiolitis (LB) and OB developed by day 30 were detected in 57% and 14%, respectively. At 90 days, all lungs showed severe allograft dysfunction with evidence of OB in 53% of cases. IL-17 expression was only detected in rats that developed acute rejection and OB. Macrophagic immunoreactivity for IL-17 was significantly increased in grafts with higher grade of acute rejection (>A2), (mean score: 1.3 vs 2.9 p Conclusions Our study demonstrates that IL-17 is overexpressed in allograft rejection mainly in more severe grade of acute rejection and in OB. Airway and endothelial cells other than inflammatory cells represent an import source of this cytokine.