Idiopathic pneumonia syndrome in mice after allogeneic bone marrow transplantation: association between idiopathic pneumonia syndrome and acute graft-versus-host disease.
OBJECTIVE
To explore the association between idiopathic pneumonia syndrome (IPS) and acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation.


METHODS
Established acute GVHD model of C57BL/6-->BALB/c mice. Chest computed tomography (CT) scans were dynamically performed in recipient mice after transplant. Lung histopathology and cytokine levels (including TNF-alpha and IFN-gamma) were examined in three experimental groups: mice receiving simple irradiation, syngeneic transplants, and allogeneic transplants.


RESULTS
All allogeneic transplant mice developed aGVHD. On CT, most aGVHD mice had bilateral diffuse lung infiltrates, while syngeneic transplant mice had normal lungs. On histopathology, aGVHD mice had acute pneumonitis. On immunohistochemistry, the infiltrates were mainly CD4+ T cells during aGVHD onset, but CD8+ T cells predominated during aGVHD progression. Lung TNF-alpha and IFN-gamma levels were higher in the three experimental groups than in normal controls on days +3 and +7 post-transplant. On day +7, TNF-alpha levels were higher in allogeneic than in syngeneic transplant mice; IFN-gamma levels were not different. On days +12 and +16, TNF-alpha levels were higher but IFN-gamma levels were lower in allogeneic mice than in syngeneic transplant mice.


CONCLUSIONS
The underlying cause of IPS is aGVHD. T cells and TNF-alpha may play a role in the pathogenesis of aGVHD-induced IPS. IPS progression may be associated with decreasing lung IFN-gamma levels.
Liu
Qifa
Q
Department of Hematology, Nanfang Hospital, Southern Medical University, Guang Zhou 510515, China. liuqifa@fimmu.com
Ning
Juan
J
Zhang
Yu
Y
Wu
Xiuli
X
Luo
Xiaodan
X
Fan
Zhiping
Z
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications* / Q000276:immunology; D054988:Idiopathic Interstitial Pneumonias / Q000150:complications* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015996:Survival Rate; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha