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Alveolar macrophage activity and the pulmonary complications of haematopoietic stem cell transplantation


BACKGROUND The success of haematopoietic (bone marrow or peripheral blood) stem cell transplantation (SCT) is compromised by pulmonary complications. We hypothesised that a proinflammatory alveolar microenvironment, reflected in alveolar macrophage (AM) cytokine production, would predispose to such complications.

METHODS AM were isolated from adult SCT recipients by bronchoalveolar lavage before SCT (n=32) and during post-transplant pancytopenia (n=23). Concentrations of tumour necrosis factor (TNF)α, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-1β, IL-6, and IL-8 in 24 hour AM culture medium were measured by enzyme linked immunosorbent assay and compared with both the occurrence of post-SCT lung disease and with subjects' previous respiratory histories.

RESULTS Eleven subjects developed lung disease within 6 months of SCT. These subjects had higher median pre-transplant AM TNFα (8 (IQR 1–8)v 2 (1–5) ng/106AM, p=0.01, median difference (D) = 3, 95% CI 0.1 to 7), GM-CSF (5 (0.7–8)v 0.2 (0.1–0.8), p=0.006, D = 4, 95% CI 0.5 to 7), and IL-6 (0.5 (0.1–1) v 0.1 (0.02–0.3), p=0.049, D = 0.3, 95% CI 0.0002 to 1) production than remaining subjects; IL-1β and IL-8 did not differ. During pancytopenia high AM GM-CSF production again predicted later lung disease (1 (0.7–9) v 0.1 (0.06–0.3), p=0.01, D = 1, 95% CI 0.1 to 6). A history of recent chest disease was associated with high AM TNFα and GM-CSF production and with post-SCT lung disease. Pre-SCT lung function was unrelated to post-SCT lung disease.

CONCLUSIONS Recent respiratory disease and persistent proinflammatory AM behaviour detectable before transplantation are associated with lung disease following SCT. These associations may prove useful in pre-transplant risk assessment.

  • haematopoietic stem cell transplantation
  • alveolar macrophage
  • cytokines

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