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
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
复制标题
DOI：
10.1182/blood.v92.7.2581.2581_2581_2589
复制
发表时间：
1998-10-01
期刊：
影响因子：
20.3
通讯作者：
Rimm, IJ
中科院分区：
文献类型：
--
作者：
Adler, H;Beland, JL;Rimm, IJ
为了进一步了解异基因骨髓移植受者疱疹病毒肺炎的发病机制，将患有移植物抗宿主病(GVHD)的移植小鼠(B10，BR--和GT；CBA)和对照小鼠(无GVHD的移植小鼠和正常CBA小鼠)鼻腔感染1型单纯疱疹病毒(HSV-1)。与感染的对照小鼠相比，感染GVHD的异基因移植受者显示出更多的瘤周单个核细胞浸润。然而，感染GVHD的同种异体移植受者肺组织中的病毒含量低于感染的对照组小鼠。模拟感染GVHD的同种异体移植受者的支气管肺泡灌洗液(BAL)中检测到高浓度的转化生长因子-β1(TGF-β1)，感染后略有升高。抗转化生长因子-β治疗GVHD的异基因移植受者显著减少了HSV-1感染后第4天肺炎的组织学证据。我们得出结论，患有GVHD的异基因移植受者(1)肺炎增加，(2)BAL液中转化生长因子-β1水平高度升高，(3)HSV-1感染后肺病毒含量减少。我们的数据表明，新发现的细胞因子(转化生长因子-β1)产生的失调可能比病毒载量更重要，导致患有GVHD的异基因移植受者HSV-1肺炎的严重性增加，(C)1998，美国血液病学会。
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-beta 1) were detected in the bronchoalveolar lavage (BAL) fluid of mock-infected allogeneic transplant recipients with GVHD, which increased slightly after infection. Anti-TGF-beta 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-beta 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-beta 1) production may be more important than the viral load for the increased severity of HSV-1 pneumonia in allogeneic transplant recipients with GVHD, (C) 1998 by The American Society of Hematology.