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 (LTx) contributes significantly to the pathogenesis of cytomegalovirus (CMV) infection and disease. In a weak allogeneic left LTx model in the rat (Fisher 344 [F344] to Wistar Kyoto [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 LTx. 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.
Department of Cardiothoracic Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany. Karla.Lehle@klinik.uni-regensburg.de
K
K
Lehle
M
M
von Suesskind-Schwendi
C
C
Diez
M
M
Michl
E K
EK
Geissler
H U
HU
Wottge
C
C
Schmid
S W
SW
Hirt
D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008168:Lung / Q000821:virology; D016040:Lung Transplantation / Q000009:adverse effects*; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D012469:Salivary Glands / Q000821:virology; D013950:Thymus Gland / Q000821:virology; D013997:Time Factors; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine