Interleukin-1 family member 9 stimulates chemokine production and neutrophil influx in mouse lungs

Am J Respir Cell Mol Biol. 2011 Feb;44(2):134-45. doi: 10.1165/rcmb.2009-0315OC. Epub 2010 Mar 18.


Interleukin-1 (IL-1) is a proinflammatory cytokine that signals through the Type I IL-1 receptor (IL-1RI). Novel IL-1-like cytokines were recently identified. Their functions in lung disease remain unclear. Interleukin-1 family member-9 (IL-1F9) is one such IL-1-like cytokine, expressed in the lungs of humans and mice. IL-1F9 signals through IL-1 receptor-related protein 2 (IL-1Rrp2/IL-1RL2), which is distinct from IL-1RI. We sought to determine if IL-1F9 acts as a proinflammatory cytokine in lung disease. IL-1F9 protein was increased in lung homogenates of house dust mite-challenged A/J mice compared with controls, and expression was seen in airway epithelial cells. The intratracheal administration of recombinant mouse IL-1F9 increased airway hyperresponsiveness and induced neutrophil influx and mucus production, but not eosinophilic infiltration in the lungs of mice. In addition, IL-1α protein levels in bronchoalveolar lavage fluid, chemokines, and chemokine-receptor mRNA expression in the lungs were increased after the instillation of intratracheal IL-1F9. Consistent with these changes, NF-κB transcription factor activity was increased in the lungs of mice challenged with IL-1F9 and in a macrophage cell line treated with IL-1F9. These data suggest that IL-1F9 is upregulated during inflammation, and acts as a proinflammatory cytokine in the lungs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / administration & dosage
  • Animals
  • Base Sequence
  • Bronchial Hyperreactivity / etiology
  • Bronchial Hyperreactivity / immunology
  • Cell Line
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • DNA Primers / genetics
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism
  • Interleukin-1 / pharmacology*
  • Lung / drug effects*
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C3H
  • Mucus / metabolism
  • NF-kappa B / metabolism
  • Neutrophil Infiltration / drug effects*
  • Neutrophil Infiltration / immunology
  • Pyroglyphidae / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology


  • Allergens
  • Chemokines
  • DNA Primers
  • Interleukin-1
  • NF-kappa B
  • RNA, Messenger
  • Recombinant Proteins