Idiopathic pneumonia syndrome after bone marrow transplantation: the role of pre-transplant radiation conditioning and local cytokine dysregulation in promoting lung inflammation and fibrosis

Pulmonary complications and graft-vs.-host disease (GVHD) remain severe thr eats to survival after bone marrow transplantation (BMT). Idiopathic pneumo nia syndrome (IPS) accounts for nearly 50% of all the cases of interstitial pneumonitis after BMT. IPS is characterized by an early inflammatory phase followed by chronic inflammation and fibrosis of lung tissue; however, the immunopathogenesis of this disease is not yet clearly understood. This bip hasic syndrome has been reported to be associated with pre-transplant radia tion conditioning in some studies while others have suggested that GVHD or autoimmune phenomena may be responsible for its development. The early post -BMT phase is characterized by the presence of inflammatory cytokines whose net effect is to promote lymphocyte influx into lungs with minimal fibrosi s, that leads to an acute form of graft-vs.-host reaction-mediated pulmonar y tissue damage. Gradual changes over time in leucocyte influx and activati on lead to dysregulated wound repair mechanisms resulting from the shift in the balance of cytokines that promote fibrosis. Using data from new animal models of IPS and information from studies of human IPS, we hypothesize th at cytokine-modulated immunological mechanisms which occur during the acute and chronic phases after bone marrow transplantation lead to the developme nt of the progressive, inflammatory, and fibrotic lung disease typical of i diopathic pneumonia syndrome.