A Role for Transforming Growth Factor-β1 in the Increased Pneumonitis in Murine Allogeneic Bone Marrow Transplant Recipients With Graft-Versus-Host Disease After Pulmonary Herpes Simplex Virus Type 1 Infection

Abstract

To gain further insights in the pathogenesis of herpesvirus pneumonia in allogeneic bone marrow transplant recipients, transplanted mice (B10.BR → CBA) with graft-versus-host disease (GVHD) and control mice (transplanted mice without GVHD and normal CBA mice) were infected intranasally with herpes simplex virus type 1 (HSV-1). When compared with infected control mice, infected allogeneic transplant recipients with GVHD showed increased periluminal mononuclear cell infiltrates. However, infected allogeneic transplant recipients with GVHD showed lower virus content in the lung tissue than infected control mice. High concentrations of transforming growth factor-beta 1 (TGF-β1) were detected in the bronchoalveolar lavage (BAL) fluid of mock-infected allogeneic transplant recipients with GVHD, which increased slightly after infection. Anti–TGF-β treatment of allogeneic transplant recipients with GVHD significantly decreased the histological evidence of pneumonitis at day 4 after HSV-1 infection. We conclude that allogeneic transplant recipients with GVHD have (1) increased pneumonia, (2) highly elevated levels of TGF-β1 in the BAL fluid, and (3) reduced pulmonary virus content after HSV-1 infection. Our data suggest that the newly recognized dysregulation of cytokine (TGF-β1) production may be more important than the viral load for the increased severity of HSV-1 pneumonia in allogeneic transplant recipients with GVHD.