Early Immune Response to Acute Gastric Fluid Aspiration in a Rat Model of Lung Transplantation

Objectives: Chronic aspiration of gastric fluid contents can decrease long-term survival of pulmonary transplants due to development of obliterative bronchiolitis. However, little is known about the early immune response and the cascade of events involved in the development of obliterative bronchiolitis. Materials and Methods: We utilized a rat orthotopic pulmonary transplant model and a single aspiration of either gastric fluid or normal saline to investigate the histologic, cellular, and cytokine changes associated with an acute gastric fluid aspiration event compared with normal saline at 2 and 10 days after aspiration. Results: Our observations included a decrease in pulmonary compliance and increased airway inflammation and acute rejection of the transplanted lung, as well as increases in macrophages, granulocytes, and proinflammatory cytokines such as interleukin 1 beta, transforming growth factor beta 1 and beta 2, and tumor necrosis factor a in bronchoalveolar lavage fluid from the transplanted lung of gastric fluid-aspirated rats compared with normal saline-aspirated rats. Conclusions: The acute inflammatory response observed in the present study is consistent with changes found in chronic models of aspiration-associated injury and suggests a potentially important role for mast cells in the development of obliterative bronchiolitis.