Idiopathic pneumonia syndrome after syngeneic bone marrow transplant in mice

Karan S. Bhalla, Rodney J. Folz

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Idiopathic pneumonia syndrome is characterized by noninfectious diffuse lung injury after myeloablative chemotherapy and bone marrow transplant. Because little is known about its pathogenesis after autologous-based regimens, we have developed a routine model that closely mimics the human lung disease process. Using an autologous regimen similar to that used for patients with metastatic breast cancer, mice developed pulmonary injury as early as 1 day posttransplant. This lung injury was most dramatically characterized by decreased lung compliance that was associated with an intense monocytic cellular infiltrate of activated macrophages. This influx was preceded by an acute elevation in monocyte chemotactic protein-1 and macrophage inflammatory protein-lα. The conditioning regimen caused substantial oxidative stress as manifest by elevations in lung lipid peroxidation and oxidized glutathione. To test the hypothesis that oxidation is directly responsible for the lung toxicity, we administered the antioxidant, n-acetylcysteine. These mice showed substantially less lung injury, thus providing direct evidence that oxidative stress plays a distinct role in the development of lung injury in the early periautologous bone marrow transplant period. Attenuation of lung oxidative stress and/or inflammation in patients undergoing autologous bone marrow transplant may reduce the subsequent development of idiopathic pneumonia syndrome.

Original languageEnglish (US)
Pages (from-to)1579-1589
Number of pages11
JournalAmerican journal of respiratory and critical care medicine
Volume166
Issue number12 I
DOIs
StatePublished - Dec 15 2002

Keywords

  • Acute lung injury
  • Inflammation
  • Interstitial pneumonitis
  • Oxidative stress

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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