Everolimus's influence on persistent acute rejection after experimental lung transplantation.

In lung transplantation, acute rejection episodes increase the risk of chronic rejection. Therefore treatment of acute rejection needs to be optimized for better long-term outcome of lung-transplantation and patient survival. The aim was to verify whether an inhibitor of the mammalian target of rapamycin (Everolimus) contained the extent of persistent acute rejection after left lung allo-transplantation in rats. Rats (F344-to-WKY) with a high grade of acute rejection were treated with methylprednisolone (10mg/kg, postoperative days 14-16) alone or in combination with everolimus (2.5 mg/kg, postoperative days 14-30). The rats were killed on postoperative day 20 and 30. Infiltration of inflammatory cells (ED1, CD11a, CD18) and activation of endothelial cells (ICAM-1) were measured by immunohistochemistry Everolimus treatment significantly reduced the number of ICAM-1 positive small vessels (66%; p<0.05) and suppressed the infiltration of leucocytes (CD11a (64%), CD18 (42%); p<0.05) and macrophages (ED1; 22%) in the allografts on POD 30. Despite this clear anti-inflammatory effects, lung allografts still showed severe acute vascular rejection in combination with high grade small airway inflammation. The shown anti-inflammatory effects of Everolimus could not delay the progression of acute rejection in rat lung allografts.