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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.

Citation

Elisabeth Brunner, Karla Lehle, Stephan W Hirt, Christof Schmid, Marietta von Suesskind-Schwendi. Everolimus's influence on persistent acute rejection after experimental lung transplantation. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2013 May-Jun;22(3):355-9

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PMID: 23828676

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