Oxidative stress and NF-κB activation: Correlation in patients following allogeneic bone marrow transplantation

Although in vitro data has linked reactive oxygen species (ROS) to activation of nuclear factor κB (NF-κB), little data exist regarding this relationship in human disease. We hypothesized that bone marrow transplantation (BMT) would impart a degree of oxidative stress that might lead to in vivo activation of the redox-sensitive transcription factor NF- κB. Because NF-κB regulates transcription of many proinflammatory mediators, we reasoned that activation of NF-κB might contribute to the development of transplant-related complications. To evaluate NF-κB activation in humans, we measured NF-κB binding activity in nuclear extracts of bronchoalveolar lavage (BAL) cells obtained before and after allogeneic bone marrow transplantation (BMT) in 7 patients. Changes in BAL cell NF-κB binding activity were compared with changes in urinary F₂-isoprostane concentration, an indicator of in vivo free radical-catalyzed lipid peroxidation. Although the extent of in vivo lipid peroxidation has substantial interindividual variability over time, we found a strong correlation between the pre/post-BMT ratio of urinary isoprostane concentrations and pre/post-BMT ratio of NF-κB binding activity in BAL cells, R = 6.96, p = 0.0005). This correlation is selective, because no relationship was found between the transcription factor CREB and urinary F₂- isoprostane excretion. Although limited by the small number of patients studied, our data link oxidant stress to NF-κB activation in human alveolar macrophages following BMT. It is possible that such interactions may contribute to the clinical course after BMT by affecting transcription of proinflammatory genes.