title: Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis.
abstract: BACKGROUND
  The purpose of this study was to characterize the relationship between tissue cytokine expression and the cellular infiltrate present in chronic hyperplastic sinusitis with nasal polyposis (CHS/NP) and to compare the immunopathology and cytokine profile of patients with allergy versus patients without allergy.
  
  
  METHODS
  Nasal polyp tissue samples from 12 patients with CHS/NP and nasal turbinate biopsy specimens from 10 normal control patients were examined for the expression of interleukin (IL)-4, IL-2, and interferon (IFN)-gamma cytokine messenger RNA (mRNA) species by in situ hybridization. These data were analyzed in conjunction with data previously reported for the cytokine mRNA species granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 and the immunocytochemical profile of the inflammatory cell infiltrate. Patients with allergy were distinguished from those without allergy on the basis of allergy skin tests.
  
  
  RESULTS
  Tissue eosinophilia was a prominent feature of both allergic and nonallergic CHS/NP and correlated in both subgroups with the density of GM-CSF and IL-3 mRNA+ cells. In comparison with normal controls, patients with allergic CHS/NP had significantly higher CHS/NP had significantly higher tissue densities of GM-CSF, IL-3, IL-4, and IL-5 (p < or = 0.025). In contrast, patients with nonallergic CHS/NP had significantly higher tissue densities of GM-CSF, IL-3, and IFN-gamma (p < or = 0.001). The allergic and nonallergic subgroups showed distinct cytokine profiles with the most distinguishing cytokines of the allergic subgroup being IL-4 (p = 0.001) and IL-5 (p = 0.017) and of the nonallergic subgroup being IFN-gamma (p = 0.004). Furthermore, patients with allergic CHS/NP showed an increased density of CD3+ T lymphocytes compared with either controls or patients with nonallergic CHS/NP (p = 0.03). The density of CD3+ T lymphocytes was the only significant difference between patients with allergic and nonallergic CHS/NP. A clinical history of aspirin sensitivity was strongly correlated with nonallergic CHS/NP, as well as the nonallergic CHS/NP profile of cytokines, including IFN-gamma.
  
  
  CONCLUSIONS
  We conclude that distinct mechanisms of eosinophilia exist in patients with allergic versus nonallergic CHS/NP. The allergic mechanism involves production of TH2-type cytokines, including GM-CSF, IL-3, IL-4, and IL-5, by infiltrating T lymphocytes. The nonallergic mechanism remains unknown but does involve production of GM-CSF, IL-3, and IFN-gamma. However, nonallergic eosinophilia is independent of IL-4 and IL-5, cytokines that contribute to tissue eosinophilia in allergic inflammation. Aspirin sensitivity is strongly correlated with nonallergic CHS/NP and production of the nonallergic CHS/NP profile of cytokines, including IFN-gamma.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Hamilos
authors.forename: D Y
authors.initials: DY
authors.lastname: Leung
authors.forename: R
authors.initials: R
authors.lastname: Wood
authors.forename: L
authors.initials: L
authors.lastname: Cunningham
authors.forename: D K
authors.initials: DK
authors.lastname: Bean
authors.forename: Z
authors.initials: Z
authors.lastname: Yasruel
authors.forename: E
authors.initials: E
authors.lastname: Schotman
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000276:immunology; D002465:Cell Movement; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004342:Drug Hypersensitivity / Q000150:complications; D004802:Eosinophilia / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications; D012333:RNA, Messenger / Q000378:metabolism; D012852:Sinusitis / Q000150:complications / Q000209:etiology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D001241:Aspirin