Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2581-2589
A Role for Transforming Growth Factor-
1 in the Increased
Pneumonitis in Murine Allogeneic Bone Marrow Transplant Recipients With
Graft-Versus-Host Disease After Pulmonary Herpes Simplex Virus Type 1 Infection
Heiko Adler,
Janice L. Beland,
Wende Kozlow,
Nadia C. Del-Pan,
Lester Kobzik, and
Ilonna J. Rimm
From the Division of Pediatric Hematology-Oncology, Dana-Farber
Cancer Institute, Department of Pediatrics, Children's Hospital,
Harvard Medical School; and the Physiology Program, Harvard School of
Public Health and Department of Pathology, Brigham and Women's
Hospital, Boston, MA.
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-
1) were detected in the bronchoalveolar lavage
(BAL) fluid of mock-infected allogeneic transplant recipients with
GVHD, which increased slightly after infection. Anti-TGF- 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-1 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-1) production may be more important than the viral
load for the increased severity of HSV-1 pneumonia in allogeneic
transplant recipients with GVHD.
