Absence of host tumor necrosis factor receptor 1 attenuates manifestations of idiopathic pneumonia syndrome

The interaction of TNF-α with TNF receptor 1 (TNFR1) activates several signal transduction pathways that lead to apoptosis or NF-κB-dependent inflammation and immunity. We hypothesized that host TNFR1 expression contributes to noninfectious lung injury and inflammation commonly observed after bone marrow transplantation (BMT), termed idiopathic pneumonia syndrome (IPS). C57BL/6 TNFR1-sufficient (TNFR1+/+) and -deficient (TNFR1−/−) mice were total body irradiated with or without cyclophosphamide conditioning and were given bone marrow plus IPS-inducing donor spleen T cells from B10.BR wild-type mice. TNFR1−/− recipient mice exhibited improved early post-BMT survival associated with decreased permeability edema. In addition, the low lung compliance measured in anesthetized, ventilated TNFR1+/+ mice on day 7 after BMT was restored to baseline during TNFR1 deficiency. Importantly, bronchoalveolar lavage fluid (BALF) inflammatory cells from TNFR1−/− vs. TNFR1+/+ mice generated less nitric oxide (·NO) and nitra...