Idiopathic pneumonia after bone marrow transplantation: Cytokine activation and lipopolysaccharide amplification in the bronchoalveolar compartment

Objective: To determine whether idiopathic pneumonia syndrome (IPS), a form of noninfectious lung injury that follows bone marrow transplantation, is associated with cytokine activation and increased susceptibility to lipopolysaccharide (LPS). Design: Case series. Setting: Tertiary referral center for marrow transplantation. Patients: Recipients with biopsy-confirmed IFS; normal volunteers and marrow transplant recipients without IFS were analyzed as controls. Measurements and Main Results: Levels of lymphocyte and macrophage-derived cytokines as well as components of the LPS, LPS-binding protein (LBP), and CD14 system in bronchoalveolar lavage (BAL) fluid were determined. We found evidence of increased vascular permeability (BAL protein) and inflammatory cytokine activation (interleukin-l, interleukin-2, interleukin-6, and tumor necrosis factor-a) in patients with IFS. Patients without IFS had BAL fluid cytokine and protein levels that were similar to levels in BAL fluid from normal volunteers, Moreover, components of the LPS amplification system (LBP and soluble CD14) were increased in patients with IFS but not in patients without IFS. Conclusions: These results provide direct evidence for proinflammatory cytokine activation in IFS and suggest that these patients might be at increased risk for LPS-mediated injury through the LBP amplification pathway.