Idiopathic Pneumonia Syndrome in Mice After Allogeneic Bone Marrow Transplantation: Association Between Idiopathic Pneumonia Syndrome and Acute Graft-Versus-Host Disease.

To explore the association between idiopathic pneumonia syndrome (IPS) and acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT).

An aGVHD model was established using a mouse transplant (C₅₇BL/6□BALB/c). Chest computed tomography (CT) scans were dynamically performed and histopathology and cytokine levels in lung tissues were kinetically detected using the Linchip system in three experimental groups: mice receiving simple irradiation, syngeneic transplants and allogeneic transplants.

The incidence of aGVHD was 100% in allogeneic transplant mice. CT revealed bilateral diffuse infiltrates in the lungs of most mice with aGVHD vs normal lung tissue in syngeneic transplant mice. Histopathology confirmed mice with aGVHD had acute pneumonitis. Immunohistochemistry showed that during aGVHD onset the infiltrates were mainly CD4⁺ T cells whereas the domination of CD4⁺ T-cell was replaced by CD8⁺ T-cell during aGVHD progression. TNF-α and IFN-γ levels within lung tissues of the three groups were higher than in normal controls on day +3 and +7 post-transplant. On day +7, TNF-α levels were higher in allogeneic than in syngeneic transplant mice, but there was no statistical difference in IFN-γ levels. On day +12 and +16, TNF-α levels were significantly higher in allogeneic than in syngeneic transplant mice, but IFN-γ levels were lower in allogeneic than in syngeneic transplant mice.

The aGVHD is the underlying cause of IPS. T cells and TNF-α may play a role in the pathogenesis of aGVHD-induced IPS. IPS progression may be associated with decreasing levels of IFN-γ within the lung tissues.

No relevant conflicts of interest to declare.