Relevance of maintenance triple‐drug immunosuppression to bridle the amplification of rat cytomegalovirus infection after experimental lung transplantation

Immunosuppressive therapy required to treat rejection after lung transplantation ( LT x) contributes significantly to the pathogenesis of cytomegalovirus ( CMV ) infection and disease. In a weak allogeneic left LT x model in the rat (Fisher 344 [F344] to W istar K yoto [ WKY ] rats) we analyzed the influence of acute CMV infection on postoperative day ( POD ) 3, with application of standard triple‐drug immunosuppression ( TD ‐ IS ) (cyclosporin A, azathioprine, prednisolone) on late outcome after LT x. Native right lungs and syngeneic grafts ( WKY to WKY ) served as controls. Rats were sacrificed on POD 15, 30, 60, and 100. TD ‐ IS completely prevented acute and chronic rejection in non‐infected rats. Allografts of CMV ‐infected rats treated with TD ‐ IS showed only mild perivascular infiltrations in 6/10 rats ( POD 15 and 30), which persisted up to POD 100 in 4/10 rats. In the long‐term course, mild isolated interstitial and alveolar changes were found in 40% of these animals. In conclusion, rat CMV infection partially neutralized the immunosuppressive effect of TD ‐ IS . However, an amplification of CMV infection under TD ‐ IS can be controlled and does not result in fatal outcome.