title: IL-1 Receptor Antagonist Inhibits Early Granulation Formation.
abstract: OBJECTIVE
  Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers.
  
  
  METHODS
  Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra-treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction.
  
  
  RESULTS
  There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-β and IL-1β between the treated and untreated specimens.
  
  
  CONCLUSIONS
  Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation.
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Nicolli
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ankona
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of California San Diego, San Diego, California, USA.
authors.forename: Sunny
authors.initials: S
authors.lastname: Haft
authors.affiliation: Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Frank
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Cecil James
authors.initials: CJ
authors.lastname: Saunders
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Noam
authors.initials: N
authors.lastname: Cohen
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA Natasha.Mirza@uphs.upenn.edu.
authors.forename: Natasha
authors.initials: N
authors.lastname: Mirza
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D006097:Granulation Tissue / Q000187:drug effects*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D007829:Laryngostenosis / Q000378:metabolism; D007830:Larynx / Q000187:drug effects* / Q000293:injuries; D051379:Mice; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000187:drug effects* / Q000293:injuries; D014135:Tracheal Stenosis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta
keywords: IL-1Ra; animal models; laryngeal stenosis; scar tissue; subglottic stenosis