IL-1beta disrupts postnatal lung morphogenesis in the mouse

Am J Respir Cell Mol Biol. 2007 Jan;36(1):32-42. doi: 10.1165/rcmb.2006-0116OC. Epub 2006 Aug 3.


Pulmonary inflammation and increased production of the inflammatory cytokine IL-1beta are associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. To study the actions of IL-1beta in the fetal and newborn lung in vivo, we developed a bitransgenic mouse in which IL-1beta is expressed under conditional control in airway epithelial cells. Perinatal pulmonary expression of IL-1beta caused respiratory insufficiency that was associated with increased postnatal mortality. While intrauterine growth of IL-1beta-expressing mice was normal, their postnatal growth was impaired. IL-1beta disrupted alveolar septation and caused abnormalities in alpha-smooth muscle actin and elastin deposition in the septa of distal airspaces. IL-1beta disturbed capillary development and inhibited the production of vascular endothelial growth factor in the lungs of infant mice. IL-1beta induced the expression of CXC chemokines KC (CXCL1) and macrophage inflammatory protein-2 (CXCL2) and of CC chemokines monocyte chemotactic protein (MCP)-1 (CCL2) and MCP-3 (CCL7), consistent with neutrophilic and monocytic infiltration of the lungs. IL-1beta caused goblet cell metaplasia and bronchial smooth muscle hyperplasia. Perinatal expression of IL-1beta in epithelial cells of the lung caused a lung disease that was clinically and histologically similar to BPD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Bronchopulmonary Dysplasia / metabolism
  • Bronchopulmonary Dysplasia / pathology*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL7
  • Chemokine CXCL1
  • Chemokines, CXC / metabolism
  • Disease Models, Animal
  • Elastin / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Infant, Newborn
  • Interleukin-1beta / genetics
  • Interleukin-1beta / physiology*
  • Lung / abnormalities
  • Lung / blood supply
  • Lung / growth & development*
  • Mice
  • Mice, Transgenic
  • Monocyte Chemoattractant Proteins / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Actins
  • CCL7 protein, human
  • Ccl2 protein, mouse
  • Ccl7 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL7
  • Chemokine CXCL1
  • Chemokines, CXC
  • Cxcl1 protein, mouse
  • Interleukin-1beta
  • Monocyte Chemoattractant Proteins
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Elastin