title: Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid.
abstract: BACKGROUND
  Allergen-induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2-type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage-colony stimulating factor (GM-CSF) may contribute to late-responses and tissue eosinophilia and is inhibitable by topical corticosteroid.
  
  
  METHODS
  Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM-CSF.
  
  
  RESULTS
  Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5-fold increase in cells expressing mRNA for GM-CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM-CSF mRNA+ cells were co-localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF.
  
  
  CONCLUSIONS
  The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM-CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM-CSF from T lymphocytes or reducing autocrine production of GM-CSF from eosinophils.
authors.affiliation: Upper Respiratory Medicine, National Heart & Lung Institute, Imperial College, London, UK.
authors.forename: K T
authors.initials: KT
authors.lastname: Nouri-Aria
authors.forename: K
authors.initials: K
authors.lastname: Masuyama
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: S
authors.initials: S
authors.lastname: Rak
authors.forename: O
authors.initials: O
authors.lastname: Lowhagen
authors.forename: E
authors.initials: E
authors.lastname: Schotman
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
authors.forename: S
authors.initials: S
authors.lastname: Durham
mesh_terms: D000281:Administration, Intranasal; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D001706:Biopsy; D004802:Eosinophilia / Q000276:immunology; D004848:Epithelium / Q000737:chemistry; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008297:Male; D009297:Nasal Mucosa / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D010919:Placebos; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016375:Antisense Elements (Genetics); D005938:Glucocorticoids; D010919:Placebos; D015347:RNA Probes; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068298:Fluticasone