title: Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma.
abstract: BACKGROUND
  IL-1 is a pleotropic cytokine that has been shown to play a prominent role in asthma induced by large-molecular-weight proteins. Increased IL-1 immunostaining in the submucosa of patients with toluene diisocyanate (TDI)-induced asthma has also been observed, suggesting that this cytokine might also be important in asthma associated with low-molecular-weight chemicals.
  
  
  OBJECTIVE
  We sought to determine the role of IL-1 signaling in airway reactivity and inflammation by using a murine model of TDI-induced asthma.
  
  
  METHODS
  C57BL/6 mice were exposed to TDI by means of vapor inhalation (20 ppb; 4 hours per day, 5 days per week, for 6 weeks) and then challenged 2 weeks later by inhalation with 20 ppb TDI vapor for 1 hour.
  
  
  RESULTS
  Sensitized-challenged mice showed increased airway hyperresponsiveness (AHR), increased levels of TDI-specific IgG1 antibodies, airway epithelial thickening, inflammation consisting of infiltrating lymphocytes and eosinophils, and increased mRNA expression of IL-4, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the lung. Prevention of IL-1 signaling through deletion of the IL-1 receptor type I or administration of neutralizing antibodies to both IL-1beta and IL-1alpha abrogated the development of TDI-induced asthma. A partial reduction in AHR and TDI-specific IgG1 levels was observed in mice administered anti-IL-1beta, whereas anti-IL-1alpha had no effect on either parameter. Antibodies to IL-1beta or IL-1alpha alone blocked airway inflammation and the expression of IL-4 and adhesion molecules in the lung.
  
  
  CONCLUSIONS
  These results suggest that IL-1 signaling is critical for AHR and airway inflammation, with IL-1beta and IL-1alpha having unique and overlapping roles in TDI-induced occupational asthma.
authors.affiliation: Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505-2888, USA. vjohnson3@cdc.gov
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Johnson
authors.forename: Berran
authors.initials: B
authors.lastname: Yucesoy
authors.forename: Michael I
authors.initials: MI
authors.lastname: Luster
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000517:prevention & control; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000517:prevention & control; D015398:Signal Transduction; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014051:Toluene 2,4-Diisocyanate