Anti-IL-23 antibody blockade of IL-23/IL-17 pathway attenuates airway obliteration in rat orthotopic tracheal transplantation

作者:Cao, Hao; Lan, Qin; Shi, Qian; Zhou, Xiaohui; Liu, Gang; Liu, Jian; Tang, Guangliang; Qiu, Chenli; Qiu, Chao; Xu, Jianqing; Fan, Huimin*; Liu, Zhongmin
来源:International Immunopharmacology, 2011, 11(5): 569-575.
DOI:10.1016/j.intimp.2010.11.007

摘要

Obliterative bronchiolitis (OB) has been a major obstacle to long-term allograft survival after lung transplantation, and the underlying mechanism is not well understood. As IL-23/IL-17 pathway has been shown to play important roles in airway inflammation, in this study we have investigated the role of IL-23/IL-17 pathway in acute and chronic airway allograft rejection. We used a rat OB model in orthotopic tracheal transplantation, and investigated the effects of anti-IL-23 blockade antibody on acute and chronic airway allograft rejection. Anti-IL-23 antibody impaired the function of IL-23 in inducing IL-17 production. The rats that received allografts and treated with anti-IL-23 antibody showed significantly less symptom of airway obliteration and chronic transplant rejection compared with control rats which received physiological saline or IgG antibody. Taken together, our results suggest that anti-IL-23 antibody is effective in protecting allograft rejection and the development of chronic OB in allo-tracheal transplantation. These findings may have implications for new therapies to prevent OB and allograft rejection in human lung transplantation.