title: Cytomegalovirus induces interstitial lung disease in allogeneic bone marrow transplant recipient rats independent of acute graft-versus-host response.
abstract: Interstitial lung disease (ILD) after allogeneic bone marrow transplantation (BMTx) is an important clinical problem in terms of diagnosis, therapy, and pathogenesis. Graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection seem to be major risk factors for ILD, but their role in the pathogenesis is not well established. We previously reported CMV-induced ILD in allogeneic bone marrow recipient rats, which was prevented by antiviral drug treatment. In this paper, we describe the pathology of ILD in allogeneic bone marrow transplant recipient rats and the relation of ILD with CMV infection and GvHD. Brown Norway rats received an allogeneic (Lewis) BMTx and rat CMV infection, after an allogeneic (Lewis) lung transplantation and immunosuppression. CMV infection was recorded by the amount of infectious virus and viral antigens in the lung. ILD was monitored by the presence of diffuse histopathologic changes in the alveolar septal wall. GvHD was scored by the relative splenic weights and the presence of perivascular infiltrates in the lung. Cells expressing CMV antigens were more numerous in the alveolar septa of the allogeneic recipient lungs than in the syngeneic donor lungs (p < 0.05). The high viral load in the recipient lung of allogeneic BMTx recipient rats was accompanied by diffuse ILD, marked by extensive microvascular damage and congestion of the alveolar septa. ILD was observed neither in the syngeneic donor lung nor in both lungs of mock-infected animals. GvHD was not observed in rat-CMV-infected or in mock-infected animals. Our results indicate that CMV induces microvascular damage, resulting in ILD. This process is independent of GvHD.
authors.affiliation: Department of Medical Microbiology, University of Limburg, The Netherlands.
authors.forename: F S
authors.initials: FS
authors.lastname: Stals
authors.forename: G
authors.initials: G
authors.lastname: Steinhoff
authors.forename: S S
authors.initials: SS
authors.lastname: Wagenaar
authors.forename: J P
authors.initials: JP
authors.lastname: van Breda Vriesman
authors.forename: A
authors.initials: A
authors.lastname: Haverich
authors.forename: P
authors.initials: P
authors.lastname: Dormans
authors.forename: F
authors.initials: F
authors.lastname: Moeller
authors.forename: C A
authors.initials: CA
authors.lastname: Bruggeman
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D003586:Cytomegalovirus Infections / Q000150:complications*; D006087:Graft vs Host Reaction; D016040:Lung Transplantation; D008297:Male; D011014:Pneumonia / Q000209:etiology; D011183:Postoperative Complications; D011658:Pulmonary Fibrosis / Q000209:etiology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew