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 lipopol ysaccharide (LPS). Design: Case series. Setting: Tertiary referral center for marrow transplantation. Patients: Recipients with biopsy-confirmed IFS; normal volunteers and marro w 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 tumo r necrosis factor-a) in patients with IFS. Patients without IFS had BAL flu id cytokine and protein levels that were similar to levels in BAL fluid fro m normal volunteers, Moreover, components of the LPS amplification system ( LBP and soluble CD14) were increased in patients with IFS but not in patien ts without IFS. Conclusions: These results provide direct evidence for proinflammatory cyto kine activation in IFS and suggest that these patients might be at increase d risk for LPS-mediated injury through the LBP amplification pathway.