Severity of elastase-induced emphysema is decreased in tumor necrosis factor-alpha and interleukin-1beta receptor-deficient mice

Lab Invest. 2002 Jan;82(1):79-85. doi: 10.1038/labinvest.3780397.


A single intratracheal dose of porcine pancreatic elastase, which is cleared from the lung by 24 hours, was administered to wild-type, IL-1beta type 1 receptor-deficient, double TNF-alpha (type 1 and type 2) receptor-deficient, and combined TNF-alpha (type 1 receptor) plus IL-1beta receptor-deficient mice. The mean linear intercept (Lm) of saline-treated mice was 32(3) microm [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) microm at 21 days versus 52(5) microm at 5 days after treatment, indicating that alveolar wall remodeling occurs long after the elastase injury. At 21 days, Lm values were 67(10), 62(3), and 39(5) microm in elastase-treated mice deficient in the IL-1beta receptor, double TNF-alpha receptors, and combined receptors, respectively. The level of apoptosis assessed by a terminal deoxynucleotidyl transferase-catalyzed in situ nick end-labeling assay was increased at 5 days after elastase treatment and was markedly and similarly attenuated in the IL-1beta, the double TNF-alpha, and the combined receptor-deficient mice. Our results indicate that inflammatory mediators exacerbate elastase-induced emphysema. We estimate that in the combined TNF-alpha + IL-1beta receptor-deficient mice, inflammation accounts for about 80% of the emphysema that develops after elastase treatment; decreased apoptosis of lung cells likely contributes to decreased severity of emphysema.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Disease Progression
  • Emphysema / chemically induced
  • Emphysema / pathology
  • Emphysema / physiopathology*
  • Emphysema / prevention & control
  • Humans
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Knockout
  • Pancreatic Elastase / toxicity*
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / physiology*
  • Receptors, Tumor Necrosis Factor / deficiency
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Reference Values


  • Receptors, Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Pancreatic Elastase