title: Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease.
abstract: BACKGROUND
  The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear.
  
  
  OBJECTIVE
  To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues.
  
  
  METHODS
  Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay.
  
  
  RESULTS
  CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P < 0.001), IL-13 (P < 0.001), eotaxin-2 (P < 0.001), and monocyte chemoattractant protein (MCP)-4 (P < 0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P < 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed.
  
  
  CONCLUSIONS
  CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Whitney W
authors.initials: WW
authors.lastname: Stevens
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ocampo
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Sergejs
authors.initials: S
authors.lastname: Berdnikovs
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sakashita
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Mahdavinia
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Lydia
authors.initials: L
authors.lastname: Suh
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: James E
authors.initials: JE
authors.lastname: Norton
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hulse
authors.affiliation: 2 Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.affiliation: 3 Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee; and.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.affiliation: 2 Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Harris
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.
authors.forename: Roderick G
authors.initials: RG
authors.lastname: Carter
authors.affiliation: 4 Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, Fukui, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: 2 Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.affiliation: 1 Division of Allergy/Immunology, Department of Medicine, and.|2 Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000328:Adult; D000368:Aged; D055963:Asthma, Aspirin-Induced / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000276:immunology; D009298:Nasal Polyps / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012220:Rhinitis / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D012852:Sinusitis / Q000150:complications / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: CRSsNP; CRSwNP; eosinophil