title: Substance P and neurokinin 1 receptors as potential therapeutic targets in children with OSA.
abstract: BACKGROUND
  Increased substance P (SP) levels and abundant expression of neurokinin (NK) 1 receptor in adenotonsillar tissues of children with OSA but not recurrent tonsillar infection (RI) suggest that NK1 antagonists could be useful in treating OSA.
  
  
  METHODS
  The effects of SP and the NK1 antagonist GR-82334 were examined on mixed cell cultures prepared from dissociated tonsils harvested intraoperatively from children with OSA and RI. Proliferation was assessed by [3H]-thymidine or 5-ethynyl-2'-deoxyuridine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-1β) was assessed in supernatants by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  SP elicited dose-dependent increases in tonsillar cell proliferation in mixed cell cultures from children with OSA but not with RI (P &lt; .0001). The NK1 antagonist exhibited dose-dependent reductions in cellular proliferative rates in OSA-derived cell cultures but not in RI-derived mixed cell cultures (P &lt; .00001). SP treatment was associated with increased TNF-α and IL-6 production, and GR-82334 abrogated SP effects, as well as reduced basal cytokine release (P &lt; .0001).
  
  
  CONCLUSIONS
  SP pathways appear to underlie intrinsic proliferative and inflammatory signaling pathways in tonsillar tissues from children with OSA but not with RI. Selective disruption of these pathways may provide nonsurgical alternatives for prevention and treatment of pediatric OSA.
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Jinkwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhattacharjee
authors.affiliation: Department of Surgery, Division of Otolaryngology, University of Louisville, Louisville, KY.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Goldman
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL. Electronic address: lgozal@peds.bsd.uchicago.edu.
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
mesh_terms: D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists / Q000627:therapeutic use; D014066:Palatine Tonsil / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010803:Physalaemin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C079014:GR 82334; D010803:Physalaemin; D013373:Substance P